Veterinary World, EISSN: 2231-0916 REVIEW ARTICLE

Available at www.veterinaryworld.org/Vol.17/November-2024/1.pdf Open Access

A review of feline infectious peritonitis virus infection

Tridiganita Intan Solikhah1 , Qurrotul Aini Dwi Agustin1 , Ratmasari Alifina Damaratri1 , Della Ayuke Fika Siwi1 ,
Ghulam Naufal Rafi’uttaqi1 , Vincent Angelino Hartadi1 , and Gahastanira Permata Solikhah2

1. Division of Veterinary Clinic, Department of Health and Life Sciences, Faculty of Health, Medicine, and Life Sciences,
Universitas Airlangga, Banyuwangi, Indonesia; 2. Cahaya Pet Clinic, Veterinarian, Mojokerto, Indonesia.
Corresponding author: Tridiganita Intan Solikhah, e-mail: tridiganita-intan-s@fkh.unair.ac.id
Co-authors: QADA: qurrotul.aini.dwi-2021@fkh.unair.ac.id, RAD: ratmasari.alifina.damaratri-2021@fkh.unair.ac.id,
DAFS: della.ayuke.fika-2021@fkh.unair.ac.id, GNR: ghulam.naufal.rafiuttaqi-2021@fkh.unair.ac.id,
VAH: vincent.angelino.hartadi-2021@fkh.unair.ac.id, GPS: gahastaniraps@gmail.com
Received: 06-07-2024, Accepted: 20-09-2024, Published online: 05-11-2024

doi: www.doi.org/10.14202/vetworld.2024.2417-2432 How to cite this article: Solikhah TI, Agustin QAD, Damaratri RA,
Siwi DAF, Rafi’uttaqi GN, Hartadi VA, and Solikhah GP (2024) A review of feline infectious peritonitis virus infection,
Veterinary World, 17(11): 2417–2432.

Abstract
Feline infectious peritonitis (FIP) is an infectious disease characterized by non-specific laboratory changes and clinical
signs. Clinical symptoms include anorexia, jaundice, fever, and weight loss. Moreover, some lesions are found in the
digestive and respiratory systems. FIP, whose virulence varies, cannot be distinguished using several diagnostic methods.
Moreover, feline coronaviruses (FCoVs) can be classified into two serotypes based on differences in their amino acid
sequences, spike (S) protein sequences, and antibody (Ab) neutralization. There are two pathotypes, namely those caused
by FCoV, which are often referred to as feline enteric coronavirus and FIP virus (FIPV). Furthermore, FIPV infection can be
caused by sub-neutralizing levels of anti-FIPV S Abs. Therefore, a supporting diagnosis is needed to confirm FIP because
there are no specific symptoms. This review aimed to provide updated information on FIP, including epizootiology, clinical
and pathological characteristics, pathogenesis, hematology, clinicopathological and imaging features, pathological features,
experimental infection, treatment and prevention, infection and immunity, animal and public health considerations.
Keywords: clinical, feline coronavirus, feline infectious peritonitis virus, infectious disease.
Introduction virus in vitro. Initially, peritoneal exudate from cell
Based on histological abnormalities, infectious cultures was employed to grow viruses in vitro, which
peritonitis in cats was initially identified as a distinct subsequently proliferated in small intestine cultures
disease in 1963 [1]. It was not until 1970 that the exact of cats. In 1979, the development and progression of
cause of this illness was identified, as viral particles a virus-causing experimental FIP inoculation in cats
were found in 12 of 25 cats with feline infectious peri- were observed in a continuous cell line of feline ori-
tonitis (FIP) [2]. The components included viruses gin. This virus is also referred to as coronavirus [3].
that induce tropicalis in macrophages, virions housed Approximately 0.3%–1.4% of cat deaths in veterinary
within vesicles and cisterns, and the Golgi apparatus. institutions are due to FIP [3–5]. FIP can be difficult
Notably, there is an absence of viral plasma mem- to diagnose due to the absence of pathognomonic clin-
brane budding and elongated cylindrical protrusions ical signs or laboratory changes, especially if there is
extending outward from the viral particle. FIP is clas- no effusion. However, given that the disease is fatal if
sified within the Coronaviridae family. The etiologies left untreated, obtaining an accurate diagnosis is crit-
of both diseases might be linked to coronaviruses and ical [1].
retroviruses, including mouse hepatitis virus (MHV) The significance of exploring FIP serves as a
and feline leukemia virus (FeLV) (FIP virus [FIPV]), foundational reference, enabling readers to conduct
as suggested by the structural similarities between research on FIP, thereby enhancing their understand-
MHV and suspected FIPV, disease parallels between ing of its various aspects. Specifically, this includes
FIP- and MHV-related conditions, and potential con- the pathogenesis theory of FIPV infection, causative
nections between the two. The confirmation of the agents, epizootiology, clinical manifestations, hema-
viral origin and elucidation of the pathogenesis of tology, clinicopathological and pathological features,
FIP took several years because of difficulties in iso- experimental research, treatment prevention, and FIP
lating FIPV from clinical cases and cultivating the immunity. This review aims to provide detailed expla-
nations concerning the pathogenesis of FIPV infection,
Copyright: Solikhah, et al. Open Access. This article is distributed causative agents, epizootiology, clinical manifestations,
under the terms of the Creative Commons Attribution 4.0 International
License (http://creativecommons.org/licenses/by/4.0/), which hematology, clinicopathology, experimental patholog-
permits unrestricted use, distribution, and reproduction in any ical features, treatment and prevention strategies, FIP
medium, provided you give appropriate credit to the original
author(s) and the source, provide a link to the Creative Commons
infection, and immunity based on diverse studies.
license, and indicate if changes were made. The Creative Commons Feline enteric coronavirus (FECV) and FIPV
Public Domain Dedication waiver (http://creativecommons.
org/publicdomain/zero/1.0/) applies to the data made available in
were initially thought to be distinct viral species.
this article, unless otherwise stated. Subsequent studies have suggested that FECV and
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FIPV are closely related viruses with different viru- FIPV is categorized into two serotypes, type I
lence traits. When FIPV FECV isolates from the same and II, depending on the antibodies (Abs) that neu-
cattery were compared with feline coronavirus (FCoV) tralize the virus: Type I and type II [15]. Serotype I
sequences from different caterers/geographical FIPV exhibits a unique S protein specific to cats,
regions, sequence analyses of the two types exhibited whereas serotype II is a combination of cat and dog
significant resemblance [4]. These findings support enteric coronaviruses [14]. Globally, serotype I FIPV
the theory that FIPV evolved from FECV through spe- is more prevalent; however, in Japan, type II viruses
cific mutations in the viral genome of infected indi- comprise >30 of 100 isolates. Furthermore, type II
vidual cats [5]. Animal tests further substantiate the variants appear more prevalent and readily adaptable
“internal mutation” theory [6]. FIP represents a small to tissue culture, whereas type I variants have a higher
proportion of F-CoV-infected cats that develop severe tendency to induce clinical FIP [16].
disease characterized by vasculitis within a syndrome
Epizootiology
of serositis and pyogranulomatous inflammation [7].
This review aimed to provide updated infor- FIP was clinically recognized before 1962 when
mation on FIP, including epizootiology, clinical and Jean Holzworth first described its clinical presentation
pathological characteristics, pathogenesis, hematol- and identified characteristic lesions under the term
ogy, clinicopathological and imaging features, patho- “Chronic fibrinous peritonitis.” The first comprehen-
logical features, experimental infection, treatment and sive study on this condition was carried out in 1966.
prevention, infection and immunity, animal and public Subsequently, FIP has been reported globally across
health considerations. five continents: North America (the United States
and Canada), Africa (South Africa and Senegal),
Causative Agent
Asia (Japan), Oceania (Australia), and Europe (Great
The virulent forms or biotypes of FECV and Britain, Ireland, the Netherlands, Germany, Belgium,
FCoV are commonly referred to as FIPV. Ferret sys- Switzerland, and France) [17].
temic coronavirus is responsible for a disease similar FIP commonly affects domestic cats younger
to FIP, whereas ECE causes epizootic catarrhal enteri- than 2 years [18]. The incidence was equal for both
tis [8]. Although the exact cause of FIPV remains male and female cats. Domestic breeds are more sen-
unknown, mutations in the FECV genome that leads sitive to FIP than other breeds. The disease affects all
to amino acid alterations in the encoded proteins are members of the Felidae family [17]. Similar cases
believed to play a significant role [9]. The term FCoV have been observed in various feline species, includ-
has been used broadly for all distinct FCoV classi- ing the African lion, mountain lion, leopard, cheetah,
fications based on antigenic properties and biolog- jaguar, lynx, serval, caracal, European wild cat, sand
ical varieties [10]. Under this classification, FCoV cat, and Pallas cat [19].
is divided into two biotypes: FIPV and FECV [11].
Clinical and Pathological Characteristics of FIP
FIPV shares similarities with feline retroviruses that
cause acute infectious sarcomas. A mutant form of this Moyadee et al. [18] identified two primary forms
virus has been detected exclusively in tumors and is of FIP: Effusive and non-effusive. The findings of this
not transmitted horizontally in nature, unlike primary study highlighted the prevalent clinical features of cats
FeLV, which is shed in various bodily excretions and with FIP, which included abdominal distension (68%),
secretions, facilitating horizontal transmission. FIPV depression (60%), dehydration (58%), anorexia
exhibits strong attachment to cells and tissues, mak- (53%), and dyspnea (42%). Effusive FIP is charac-
ing fecal or urine discharge possible only under rare terized by fluid accumulation in the abdomen, pleura,
circumstances [12]. and/or other body cavities, such as the pericardial cav-
The genetic compositions of FCoVs share simi- ity, renal subcapsular space, scrotum, and heart due to
larities with the genetic materials. The average RNA increased vascular permeability caused by blood ves-
strand comprises approximately 29,000 nucleotide sel inflammation. Cats may exhibit symptoms such
units. The dataset includes 11 potential open read- as dyspnea and abdominal distension. These clini-
ing frames (ORFs) or genes. These consist of repli- cal features stem from the vascular and perivascular
cated non-structural components featuring two major alterations provoked by the virus, which manifest in
ORFs: Four structural ORFs responsible for coding two primary evolutionary forms: “Wet” or exudative
spike (S), coat, membrane, and nucleocapsid proteins and “dry,” which lacks fluid accumulation in cavi-
and five accessory ORFs identified as 3a-c and 7a,b. ties. The wet form involves general alterations (fever,
Notably, the presence of Gen 7a does not appear cru- apathy, and weakness), dyspnea, exudative peritonitis
cial for virulence, as evidenced by the observations of (enlarged abdominal volume, positive abdominal bal-
FECV and FIPV field strains lacking the functional 7a loon test, inflammatory fluid on peritoneal puncture
gene [13]. The role of the mutated 7b gene differs, but with total protein exceeding 3 g/dL), and high mor-
minor deletion mutations in 7b gene were identified tality. Conversely, the dry form represents chronic
in 8 of 32 associated isolates related to enteric, infec- progression with atypical symptoms that vary based
tious, and FIP conditions [14]. on primary location. In cases with nerve involvement,
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functional neurological signs are predominant, nota- head tilt, head tremors, and seizures. Conversely, the
bly behavioral changes (apathy) and motility issues physical examination revealed a thin body, abdomi-
(otolaryngological weakness, paresis, paralysis of the nal distension, dehydration, and pallor. Neurological
hind limbs, or convulsions) [20]. examination showed head tremors, head tilt, ambu-
According to research conducted by Yin latory tetraparesis, vestibular ataxia, and ambulatory
et al. [21], cats suspected of having FIPV exhibit clin- paraparesis. Three distinct neurological syndromes
ical symptoms, such as pleural effusion; some also were identified: T3-L3 myelopathy without obvious
display ascites, weight loss, lethargy, and lack of appe- brain involvement, central vestibular disease, and
tite. Jaundice and fever are additional clinical symp- multifocal CNS disease accompanied by tetraparesis.
toms associated with the virus [22]. The study results Figure-1 presents gross lesions of FIP [25].
of Moyadee et al. [18] indicated that FIP-affected Figure-2 presents an ultrasound image of ascites,
cats predominantly presented with symptoms, includ- a radiograph of a large amount of effusion in the
ing abdominal distension, depression, dehydration, abdominal cavity, necrotic foci in the kidneys, asci-
anorexia, dyspnea, jaundice, diarrhea, and vomiting. tes and enlarged lymph nodes, and interstitial nephri-
These cats exhibited decreased levels of blood urea tis [21]. Figure-3 presents feline small intestine with
nitrogen, creatinine, and albumin but increased levels extensive thickening of the intestinal wall character-
of globulin relative to the reference interval. FIP can ized by dense, white, irregularly proliferating tissue
manifest as two primary clinical forms – wet and dry that extends through the intestinal wall [26]. Figure-4
– that may sometimes overlap. The wet form is char- presents abdominal effusion from a feline infectious
acterized chiefly by the accumulation of protein-rich peritonitis cat. [26]. Figure-5 presents cat lung organ
fibrin fluid in the body cavity, which leads to symp- with severe, acute, diffuse fibrinous pleuritis [23].
toms indicative of severe and acute hypovolemia and/ Figure-6 presents feline liver pyogranulomatous
or organ compression within the affected cavity, such hepatitis with intracellular positivity [23]. Figure-7
as dyspnea and reduced peristalsis. Conversely, the presents kidney organs of FIP cats experiencing gran-
clinical manifestations of dry form depend primarily ulomatous nephritis with positive presence of intracel-
on the site of granulomatous lesion formation, most lular and extracellular granules [23].
often the kidneys, resulting in clinical and labora- Notably, some clinical symptoms are uncommon,
tory signs of renal dysfunction. However, extra-renal such as those affecting the male genitalia – specifi-
symptoms may also manifest if granulomatous lesions cally, scrotal enlargement due to peritonitis spreading
are widespread in other organs, such as the liver, lungs, to the tunica surrounding the testicles and resulting
intestines, and notably, the eyes and central nervous in edema (Figure-8) [16]. In most cases, all clinical
system (CNS) [23]. signs were identified simultaneously; however, there
According to a previous study by were instances in which neurological involvement
Crawford et al. [24], the clinical symptoms observed was not clear until the later stages of the disease.
in cats with FIP include ataxia, lack of appetite, Although most cats exhibited symptoms indicating a

a b

c d e f
Figure-1: (a–f) Gross lesions in feline infectious peritonitis (FIP). Wet FIP is represented by serofibrinous and granulomatous
serositis and granulomatous lesions in the liver (arrows). (b–f): Cats with dry FIP. Enlargement of mesenteric lymph nodes
due to granulomatous inflammation. Jejunum with multiple granulomas in the serosa. Jejunum with small subserous
granulomatous lesions in the veins (phlebitis and/or periphlebitis; arrows). Kidney with granulomatous and periphlebitis of
the capsular vein (arrow). (f): Brain with multifocal granulomatous phlebitis and periphlebitis of the cortical leptomeningeal
vein (arrow) [25].

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a b

c d
Figure-4: Abdominal effusion from a feline infectious
peritonitis cat. Non-degenerated neutrophils with
vacuolated hyperbasophilic cytoplasm (dashed arrow), two
mesothelial cells (thick arrow), and scattered erythrocytes
(thin arrow) embedded in a granular proteinaceous
eosinophilic background [26].
e f
Figure-2: (a) Ultrasound image of ascites. (b) Radiograph
of a large amount of effusion in the abdominal cavity.
(c) Presence of necrotic foci in the kidneys. (d) Ascites
and enlarged lymph nodes. (e) Interstitial nephritis is
characterized by inflammatory cell infiltration, including
macrophages, lymphocytes, neutrophils, and plasma.
(f) Presence of macrophages in the kidney using
immunohistochemical staining [21].

Figure-5: Cat lung organ with severe, acute, diffuse

fibrinous pleuritis accompanied by scattered inflammatory
cells [22].

the following findings: Fever, palpably enlarged lobu-

lated kidneys, pale mucous membranes, despondency,
and anorexia [27].
Ocular manifestations of FIP are significantly
more common, and in certain cats, they are the ini-
tial complaint. Specifically, the blood-aqueous barrier
breaks down, causing fibrin to leak into the ante-
Figure-3: Feline small intestine with extensive thickening rior chamber from vein blood vessels. Exudation
of the intestinal wall characterized by dense, white,
irregularly proliferating tissue that extends through the of either white blood cells (hypopyon) or red blood
intestinal wall [26]. cells (hyphema) into the anterior chamber is indic-
ative of uveitis and a significant breakdown of the
widespread CNS disease, three showed neurological blood-aqueous barrier. Miosis, or constriction of the
abnormalities, suggesting localized involvement. The pupil, is caused by stimulation of the iris sphincter
most commonly observed neurological symptoms muscle after prostaglandin release during uveitis.
were convulsions, nystagmus, and posterior paresis. The complaint may be a subtle or noticeable alter-
All cats either died in the hospital or were euthanized ation in the color of the iris, particularly in patients
at the owner’s request. Most affected cats exhibited with chronic anterior uveitis. Notably, ocular hypot-
not only neurological and visual impairments but also ony is caused by a decrease in aqueous humor out-
signs of systemic involvement. Medical histories and put, resulting in lower intraocular pressure than
physical examinations often revealed one or more of normal [28]. Figure-9 shows FIP-related retinal
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Figure-9: Feline infectious peritonitis-related retinal

Figure-6: Feline liver pyogranulomatous hepatitis with hemorrhage and detachment [29].
intracellular positivity [22].

Figure-10: Histopathologic slice of the eye. Mononuclear

infiltration in the choroid and exudative retinal detachment
are visible as fluid in the subretinal gap separating the
Figure-7: Kidney organs of feline infectious peritonitis retina from the choroid [29].
cats experiencing granulomatous nephritis with positive
presence of intracellular and extracellular granules [22].
and immunohistochemical characterization of feline
infectious peritonitis lesions, Fibrous exudation with
diffuse serosal inflammation, Renal granuloma devel-
opment, Numerous red cells or monocytes/macro-
phages in the same inflammatory region as seen in,
Numerous monocytes/macrophages (red cells) within
the same granuloma as shown in, Plasma cells and a
multinucleated giant cell (upper right corner) within
a type A lesion in the liver, Inflammatory cells (pre-
sumably macrophages) containing feline coronavirus
(FCoV) antigen (red cells) within an intestinal granu-
loma. FCoV-positive granules are also present extra-
cellularly (Figure-11) [30].
The classic features of FIP include the onset of
effusion in the abdominal or thoracic cavity. In addi-
tion, it presents clinical symptoms of endothelial dys-
Figure-8: The kitten’s stomach is very distended and function and vasculitis, with lesions characterized
accompanied by effusive feline infectious peritonitis. There by edema and perivascular infiltration, vessel wall
is also an enlarged scrotum due to inflammation of the degeneration, and endothelial proliferation [28].
tunica [16].
In the lungs, three primary gross patterns of dam-
age were observed. Of the 66 cats studied, 18 exhib-
hemorrhage and detachment [29]. Mononuclear infil- ited a yellow to reddish liquid, fibrillar, gelatinous, or
tration in the choroid and exudative retinal detachment is pasty substance in their thoracic cavities that adhered
visible as fluid in the subretinal gap separating the retina to both the parietal and visceral pleura. Importantly,
from the choroid (Figure-10) [29], Histopathological there were no inflammatory parenchymal changes,
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a b
a b

c d

c d

e f
Figure-12: (a-f) Feline infectious peritonitis in the lungs
of cats [28].
e f
Figure-11: Histopathological and immunohistochemical
of viral infections. This study observed vasculitis
characterization of feline infectious peritonitis lesions. and immune complex deposition. Clinically, effu-
(a) Fibrous exudation with diffuse serosal inflammation. sive (wet) and non-effusive (dry) manifestations of
(b) Renal granuloma development (type B lesion).
(c) Numerous red cells or monocytes/macrophages in the
FIP are evident. The effusive type is characterized
same inflammatory region, as seen in (a). (d) Numerous by fluid accumulation in bodily cavities, fibrinous
monocytes/macrophages (red cells) within the same pleuritis, and peritonitis. In the non-effusive form,
granuloma, as shown in (b). (e) Plasma cells and a pyogranuloma may develop in the eyes, lungs, CNS,
multinucleated giant cell (upper right corner) within a
type A lesion in the liver (cat no. 6). (f) Inflammatory
and abdominal viscera. Approximately 75% of clini-
cells (presumably macrophages) containing feline cal cases were effusive, whereas the remaining 25%
coronavirus (FCoV) antigen (red cells) within an intestinal were non-effusive. Some cats exhibited symptoms
granuloma. FCoV-positive granules are also present
consistent with both types of FIP. An exuberant form
extracellularly. Stainings: (a, b, and e): hematoxylin-eosin,
(c and d): lectin immunohistochemistry, and (f): FCoV arises when there is a strong host humoral immune
immunohistochemistry. Magnifications: (a–d): 100×, response and a weak cell-mediated immunological
(e): 400×, and (f): 200× [30]. response. Conversely, a non-effusive form develops in
response to an inflammatory response [31]. Viral fac-
and the pulmonary parenchyma was irregularly pleu- tors are critical in the pathophysiology of FIP. It has
ral and diffusely atelectasis (Figures 12a and b) [28]. been established that the S glycoprotein of FCoV con-
Similarly, the visceral and parietal pleura of the 13 trols host cell entry, and mutations in the S gene affect
cats exhibited a noticeable deposit of similar yellow cell tropism. Comparisons between FCoV excreted in
liquid, fibrillar, gelatinous, or pasty material. In these the feces of clinically “healthy” cats and FCoV from
cases, the lung parenchyma often remained intact, FIP tissues reveal more frequent mutations at various
featuring many white nodules sporadically spaced a positions within the S gene. This observation led to
few millimeters in diameter throughout the lung lobes the hypothesis that some of these mutations may serve
(Figures-12c and d) [28]. Furthermore, in 23 addi- as useful markers for distinguishing between cats
tional animals, there was little to no accumulation of with and without FIP. Nevertheless, a recent compre-
yellowish fibrillar debris in the thoracic cavity. Some hensive study indicated that one of these mutations,
showed impressions of the ribs, and the lung lobes related to a fusion peptide, is more indicative of sys-
were not deflated. Notably, the lung parenchyma temic FCoV infection than FIP itself. Systemic FCoV
frequently exhibited a noticeable pallor and several infection was observed in FCoV-viremic cats, both
sporadically scattered white nodules, each a few mil- with and without FIP, at equal frequencies [32].
limeters in diameter (Figures-12e and f) [28]. Target macrophages and monocytes are exposed
to FIPV through initial surface binding, followed by
Pathogenesis
internalization through clathrin- and caveolae-inde-
The pathogenesis of FIP involves immune pendent and dynamin-dependent endocytosis [16].
complex formation and Ab-dependent enhancement The most important step in the viral life cycle is virus
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entry into the cell. In FIPV, viral entry into cells occurs potential genes have been linked to this virulence
through two mechanisms. The first pathway involves shift. Irrespective of virulence, a recent study by
cytosolic entry through early endosomes (FCoV-II) Tasker et al. [7] has shown that FCoV S protein muta-
and the second through late endosomes (FCoV-I). tions indicate systemic dissemination of the virus.
Hartman et al. [33] revealed that the cellular receptor After a few days, experimental cats infected with
of FCoV-II is aminopeptidase N (APN), which binds either the prototype serotype II FIPV 79-1146 strain
to S proteins and mediates viral internalization into or a recombinant variant of this virus developed fever
cells. However, no relevant studies have investigated and rapidly lost weight. Viral RNA was detected in
FCoV-I cell receptors. FCoV binds to these receptors the feces and blood early after infection, and serum
and requires cytoplasmic access for replication. The S Ab titers increased rapidly, remaining high throughout
protein is cleaved by cathepsin B and fuses with the the illness. In other cases, diseased cats appeared to
endosomal membrane following endocytosis of the recover after the first week [36]. A previous study by
complex between the viral receptor and viral S pro- Chang et al. [37] on the pathophysiology of FIP has
tein. The fusion peptide of the S protein is located in focused on the S gene. The binding of receptors and
the S2 domain. FCoV-I possesses two specific activa- entry of the virus depend on the coronaviral S protein.
tion sites: S1/S2, which is cleaved by furin-like prote- The biotype flip may result from mutations in S gene
ase and S2’, which is cleaved by cathepsin B. FCoV-II alone or in conjunction with alterations in other genes
contains only the S2’ site, which is cleaved by cathep- because the FECV-FIPV transition involves a shift in
sin B. Cathepsin B is likely the most crucial protease target cell tropism. Recent research has explored the
facilitating FCoV entry, with cathepsin L playing a role of S gene mutations in the pathophysiology of FIP
probable secondary role. FCoV replication occurs rap- to address this issue. Most FIPVs can be distinguished
idly, and the cycle is completed in <24 h. Mutations in from FECVs by two-point mutations in the S gene,
the FCoV S gene contribute to the shift in cell tropism according to an analysis of 11 full-length genome
and pathogenicity. Following oral-fecal transmission, sequences for FECV and FIPV [37].
FCoV initially infects the intestinal tract and may dis-
Hematology
seminate to other areas, causing monocyte-associated
viremia [33]. Coronaviridae possess a single-stranded RNA
These antigen-Ab complexes are believed to be genome. There are two serotypes in the FCoV divi-
identified by macrophages but are not delivered to sion; Serotype I is the serotype found in cats. Strong
killer cells as they should be, preventing them from pleocytosis (>100 cells/mL), high protein con-
being eliminated. The outcomes of immunological centrations (>200 mg/dL), and FCoV Ab titers of
complex formation in cats depend on the antigen >1:25 were observed in an analysis of FIP-infected
content, Ab concentration, and size of the complex. cats [38]. Serotype II is the evolutionary result of
Moreover, immune complex deposition most likely a recombination event between FCoV and canine
occurs at blood vessel bifurcations, which are loca- enteric coronavirus, resulting in a chimeric FCoV
tions of high blood pressure and turbulence. FIP encoding the canine coronavirus spike gene [38].
lesions are frequently found in the kidney, uvea, and Macrophages, the primary FIPV target cells, may
peritoneum and are characterized by turbulence and penetrate the mucosal barrier and disseminate the
elevated blood pressure [34]. There is no information virus throughout the cat. Moreover, a correlation was
on the precise viral genetic factors associated with observed between the in vivo virulence of FIPV and
FIPV pathogenesis. According to the in vivo mutation its ability to affect macrophages in vitro. It has been
transition theory, virulence develops through de novo proposed that humoral immunity may not be as effec-
virus mutations occurring in vivo. A previous study tive in defending cats against FIPV as robust cell-me-
by Brown et al. [35] indicated that sequence varia- diated immune responses [39].
tions in the S protein, non-structural protein (NSP) FIP often leads to hematological irregularities,
7b, and NSP3c are disease determinants; however, the including lymphopenia, neutrophilia, anemia, and
specific type of mutation causing disease has not yet thrombocytopenia. Moreover, serum biochemical
been identified. FIP is a systemic illness that mani- anomalies commonly associated with FIP include
fests as either “wet” or effusive FIP, characterized by hyperproteinemia, hyperbilirubinemia, hyperglobu-
cavitary effusions, or as “dry” or non-effusive FIP, linemia, and hypoalbuminemia. Hyperglobulinemia is
characterized by granulomatous lesions and/or vascu- also observed in conditions such as lymphoma, mul-
litis. These two pathotypes have long been considered tiple myeloma, and persistent infections [40]. When
independent viral species. cats with FIP exhibit hyperglobulinemia (mostly
Nevertheless, molecular research has demon- gamma globulins), hypoalbuminemia (primarily
strated that they are two virulence-varying forms of hypoalbuminemia), or both, hyperproteinemia fre-
the same virus. Consequently, variations in intesti- quently manifests as a common laboratory anomaly.
nal strains have been proposed as responsible for the Moyadee et al. [41] identified hyperglobulinemia and
differing pathogenicity. No mutation has been iden- hypoalbuminemia in cats with FIP, but no increase in
tified as a definitive cause of FIP, although several total protein levels was observed. Only 17.5% of cats
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with FIP exhibit hyperproteinemia, and effusive FIP that is challenging to differentiate genetically from
is less likely than non-effusive FIP to increase total FECV; thus, further diagnostic tools are required [23].
blood protein [41]. Hyperglobulinemia may occur Despite the similarities in the epidemiological and
independently or concurrently with hypoalbuminemia virological characteristics of these two infections, the
and hyperproteinemia. Hypoalbuminemia and hyper- pathophysiology of the illness distinctly differs from
bilirubinemia are frequently associated with effusion, that of severe acute respiratory syndrome corona-
whereas azotemia is common in cats without effusion virus 2 (SARS-CoV-2). This difference starts at the
[42]. Clinically, affected patients may exhibit various cellular entry level, which is prompted by binding
symptoms depending on the organ system involved. SARS-CoV-2 to the human angiotensin-converting
These include elevated serum levels of liver enzymes enzyme 2 (ACE2) receptor [22]. Additional diagnos-
and bilirubin, increased serum urea nitrogen and creat- tic approaches include the use of magnetic resonance
inine, elevated fibrinogen levels, reduced packed cell imaging (MRI) in cats exhibiting neurological symp-
volumes, neutrophilia, lymphopenia, and proteinuria. toms of FIP [23]. MRI can identify FIP through signs
When FIP affects the CNS, cerebrospinal fluid (CSF) of ventricular dilatation in cats, a condition known
analysis often shows increased cellularity and protein as ventriculomegaly [46]. The extent of contrast
content [3]. Ab testing does not differentiate between enhancement variations correlates with the degree of
FECV and FIPV, and Ab titers are unreliable indicators ventricular dilatation. Epididymitis, multifocal hepa-
of FIP. Although most cats have Abs against FCoV, titis, and secondary obstructive hydrocephalus have
they do not necessarily develop FIP. Importantly, Abs also been observed in MRI findings [47].
against the FCoV 7b protein can be detected, assum- Abdominal ultrasound is used to detect potential
ing that FIPV includes the 7b gene [42]. Typically, abnormalities, including abdominal effusion (noted in
effusion tests offer more accurate predictive values 75% of cases) and irregularities in the kidneys (69%),
than blood tests [23]. Clinical pathological histories, lymph nodes (56%), and/or liver (37%) [48]. Feline
such as full blood and serum biochemical profiles and infectious peritonitis in a 12-year-old female cat showed
investigations of effusion or CSF are essential for FIP an anechoic peritoneal effusion (Figure-13) [48].
diagnosis [43]. Leukopenia may accompany diarrhea. The small
Blood samples from cats were drawn into vac- intestinal epithelium is a target of FECV [8]. Staining
uum blood collection tubes without anticoagulant, of the spleen, liver, brain, lymph nodes, lungs, gut, and
stored at 4°C overnight, and centrifuged for 10 min at kidney slides with hematoxylin-eosin reveals granu-
1000× g [44]. The serum was then kept cold until fur- lomatous and pyogranulomatous lesions [49]. In the
ther use. The Antech Veterinary Diagnostic Laboratory context of ascites etiology in cats, abdominal disten-
employs an automated cell counter to evaluate fresh sion is more common than neoplasia, cardiovascular
whole blood and complete blood counts [23]. The fail- disease, or hepatic or renal disease, and it is the most
ure to directly detect FIPV antigens in blood using Abs frequent physical finding in cases of wet FIP. Upon
may be due to low levels of viremia [45]. Serum chem- abdominal exploration, up to 1 L of yellow-tinged,
istry tests play a crucial role in the detection of FCoV slightly to moderately cloudy mucinous fluid is typ-
during various infection phases. Cats showing the ically found [16].
clinical signs of infectious peritonitis underwent poly- Brain lesions are a consequence of FIP infection,
merase chain reaction testing. Both serum chemistry including either meningoencephalitis or meningomyeli-
tests and the EvaGreen real-time reverse transcription tis. Stomach lesions are prevalent in the intestine [43].
polymerase chain reaction (RT-PCR) assay were used Spinal cord abnormalities were detected by MRI of the
to detect FIPV, which leads to hyperglobulinemia. patient’s brain. Observable abnormalities include ven-
A real-time PCR test using EvaGreen targeting the triculomegaly, which is characterized by enlarged ven-
highly conserved N gene was developed to screen for tricles in cats. Periventricular hyperintensity indicates
FCoV in cats. For a definitive diagnosis, viral antigens interstitial edema. The significant aspects of this imag-
in cat monocytes must be stained with immunohisto- ing procedure include cerebellar herniation, ventricu-
chemical dye [44]. Pedersen [8] has shown that FIP lar dilatation, and meningeal and ependymal contrast
cats exhibit a higher ratio of peripheral blood surface enhancement, even when obstructive hydrocephalus is
immunoglobulin-positive cells to CD21+ cells than highly improbable [24]. Hydrocephalus, which arises
specific-pathogen-free cats. Furthermore, an increase from ependyma and choroid pathologies, has been
in the number of cells expressing the plasma cell mas- recorded and may lead to convulsive disorders, demen-
ter gene encoding B lymphocyte-induced maturation tia, or personality changes, such as rage, aggression,
protein is noted [8]. hiding, or withdrawal. Vestibular cerebellar symptoms,
such as circling, head tilting, and nystagmus, also arise
Clinicopathological and Imaging Features
from FIP [16]. The clinical manifestations of CNS
The two biotypes of FCoV are FECV and FIPV. involvement in cats with dry FIP differ according to
Both biotypes are pathogenic; however, they differ in severity, specific location within the nervous system,
their infection mechanisms in cats and their poten- and organ involvement [16]. FIPV is mutagenic and can
tial to cause FIP [40]. FIP is a serological disease disseminate through the bloodstream. Both effusive and
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Pathological Features
FIP is a systemic illness characterized by gran-
ulomatous lesions (“dry” or non-effusive FIP) and/or
vascular disease. This may lead to cavitary effusions
(often called “wet” or effusive FIP) [22]. Effusive FIP,
the more traditional and prevalent form, typically pro-
gresses rapidly, accumulating fluid in the peritoneal and
a b thoracic cavities. Conversely, the “dry” or granuloma-
Figure-13: Feline infectious peritonitis in a 12-year- tous variant has a more insidious onset with extensive
old female cat: a longitudinal ultrasound image of the granuloma formation across multiple organs rather than
abdomen (case 9). (a) Between the calipers, a slightly
thickened section of the parietal peritoneum is visible
cavitary effusion [55]. The symptoms of FECV infec-
(2.6 mm). (b) The hyperechoic mesentery presents tion can emerge anywhere from 10 to 15 days to several
an uneven and nodular appearance (between calipers: months after infection. The disease progresses from a
1.2 cm). Furthermore, an anechoic peritoneal effusion subclinical state to a clinical state without improve-
(asterisk) is observed [48].
ment [56]. The lesions include hepatitis/capsulitis,
pancreatitis, ascites or abdominal effusion, serositis/
granulomatous multisystemic inflammatory responses leiomyositis, lymphadenitis, jaundice, perivasculitis,
are triggered by the replication of this mutation in mac- and uveitis. In addition, necrotizing interstitial nephri-
rophages. In patients with granulomatous FIP, the body tis has been noted in the kidneys [57]. Natural occur-
cavity lacks an inflammatory exudate. Granulomatous rences include nodules on the renal medulla surface and
FIP is a distinct clinical manifestation of the exuberant coarse lesions with grayish-white patches. Detachment
form. Small granulomas form around the arteries and of the parenchyma from the renal capsule poses a chal-
venules of the CNS in this type, affecting the CNS. The lenge. Variability in granule size has been noted in the
virus induces a cellular inflammatory response around brain. The lesions observed were parts of the third and
CNS arteries and venules, leading to the formation of fourth ventricles which were lateral ependyma and lep-
tiny granulomas. Periventricular vasculitis results in tomeningea. The inner layers of the cornea, iris, cili-
periventricular reactive astrocytosis and exudation of ary bodies, choroid membrane, and occasionally the
cells and proteins [50]. retina exhibit signs of cerebral changes. Experimental
There is only one published report by Park autopsies revealed small focal clusters of neutrophils
et al. [51] on a cat diagnosed with diffuse lung consol- and large mononuclear cells. Within the granulomas,
idation, pyogranulomatous pneumonia, and non-effu- large mononuclear cells, along with neutrophils, lym-
sive FIP. In this case, numerous masses were noted phocytes, plasma cells, and fibrin, are present and show
in the pleura, lung, and kidney, along with recurrent central necrosis [58].
granulomatous changes. Cats with the effusive form of Pneumonia is not a common characteristic of FIP.
FIP often develop small bowel disease. Typically, the The presence of pneumonic lesions indicates the poten-
radiographic hallmark of pneumonia includes alveolar tial for simultaneous infection by microorganisms. For
infiltrates on air bronchogram; however, pneumonia example, groups of coccoid and Gram-negative bacte-
resulting from bite wounds or foreign bodies may also ria in aggregate form may be distributed in the respi-
produce mass-like lesions adjacent to the lung or pleu- ratory tract and cause inflammation in affected cats.
ral wall [51]. Common symptoms in kittens include The collection of bacteria and foreign bodies may be
pneumonia, pleurisy, and hepatitis. In cats with FIPV, observed in the bronchi, often accompanied by aspi-
immune complex formation or migration of macro- ration pneumonia [38]. Furthermore, necrosis in the
phages/monocytes into the synovium, leading to gen- stellate and arcuate veins was observed in the kid-
eralized synovitis [16]. Definitive confirmation of FIP neys, along with intimal neutrophil aggregation and
necessitates the detection of the virus within lesions or granulomatous lesions, suggesting perivascular lesion
effusions. Certain clinical or clinicopathological find- development. An early-phase granulomatous lesion
ings strongly suggest the presence of FIP [23]. was identified. Granuloma formation in intralobular
To support the diagnosis of non-effusive FIP, venous adventitia is evident in lung lesions. Small
RT-PCR can be used alongside biochemical, serologi- blood vessels have been observed in the brain and lep-
cal, and hematological assessments [52]. FIPV cannot tomeninges [58]. The following pathological features
be conclusively identified using serological methods were obtained from the typical gross postmortem
alone; hence, hematological and serum biochemical observations of FIP cases. Granulomatous lesions,
tests are also performed. The RT-PCR method can be organ serosa, and fibrinous plaques can be observed
used to diagnose FIPV. Suitable specimens include within the thoracic or abdominal cavity. The mesen-
body cavity fluid (a cyst and pleural effusion), CSF, teric lymph nodes, liver, spleen, kidneys, intestinal
blood, and tissue. Using CSF can lead to highly spe- surfaces, diaphragm, and wall of the abdominal peri-
cific RNA detection [53]. Tissues suitable for RT-PCR toneum were examined. In severe cases, the peritoneal
analysis include liver, kidney, and spleen samples [54]. and/or pleural cavities may contain yellowish, viscous
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fluid, and fluid accumulation may also be noticeable and (2) by evaluating a delayed-type hypersensitiv-
in the pericardium [59]. ity reaction to FIPV. The FIPV-79-1146 and Nor15
Experimental Infection
strains exhibited similar levels of contagiousness and
were transmitted through both oral and parenteral
In an experimental setting, cell fusion was con- routes of exposure. However, isolates, such as FIPV-
ducted 6 times using mouse spleen cells immunized UCD3 and -UCD4, demonstrated similar transmission
with the FIPV strain 79-1146. Seven monoclonal Abs effects when administered orally or intraperitoneally
(mAbs) capable of neutralizing FIPV strain 79-1146 but showed significantly higher virulence when deliv-
were isolated and designated 5-6-2, 5-7-2, 6-1-1, 6-4- ered orally. In contrast, FIPV-UCD1, which is known
2, 7-1-1, 7-3-1, and 7-4-1. The polypeptide specific- for its relative malignancy, displayed lower infectivity
ity of these Abs was determined by western blotting. when administered orally than when administered par-
A competitive protection test was conducted to inves- enterally. Despite being extremely contagious through
tigate variations in epitope specificity among the seven oral and intraperitoneal routes, FIPV-UCD2 has lost
neutralizing Abs. Furthermore, the reactivity of the virulence. Hence, virulence and infectivity are distinct
mAbs that recognize the three neutralizing epitopes factors that operate independently [62].
in FIPV strain 79-1146 with feline, swine, and canine
Treatment and Prevention
coronaviruses within the same class was assessed
using a neutralization test (NT). These mAbs did not FIP is a global disease that affects domestic and
neutralize the six FIPV type I strains but did neu- wild felids. Although much research has been con-
tralize the FECV 79-1683 strain, a swine and canine ducted on FIP, it remains one of the most prevalent
coronavirus. Notably, the mAbs targeting epitope III and fatal infectious diseases in cats [21]. As clinical
(6-1-1 and 6-4-2) demonstrated excellent neutraliz- indications worsen, compassionate euthanasia in shel-
ing efficacy against this virus, including FIPV strain ter settings is a suitable method to end suffering [63].
79-1146. In addition, the NT was used to evaluate the The immunosuppressive macromolecule cyclosporine
reactivity of three neutralizing mAbs (55-2, 38-1, and A (CsA) interacts with chaperone proteins known as
66-A) generated using the transmissible gastroenteri- cyclophilin, facilitating the cis/trans conformational
tis virus (TGEV) strain TO-163 as an immunogen shift of proline residues. The interaction of CsA with
against cat, dog, and swine coronaviruses. All three abundant cellular cyclophilin likely contributes to
mAbs recognize distinct epitopes of the TGEV S pro- its antiviral effect. CsA exhibited dose-dependent
tein [60]. Viruses were detected in the oropharyngeal cytotoxicity at high concentrations (cytotoxic con-
secretions and feces of all FIPV-inoculated cats. In all centration of 50% [CC50] of 14.1 µM) and inhibited
cases, viral shedding was observed in the oropharynx FIPV in fwcf-4 cells at concentrations from 0.16 to
on the 2nd day after infection and persisted until the 10 µM during post-infection therapy. CsA therapy
9th or 10th day. Most animals had a brief second oro- was administered to a client-owned cat suffering from
pharyngeal discharge on day 14 in conjunction with severe FIP, with dosages ranging from 25 mg/kg to
the emergence of clinical symptoms. Cats infected 75 mg/kg. The cat died of respiratory failure 264 days
with FIPV exhibited a rapid increase in Ab titers in after the initiation of therapy. The symptoms and effu-
the indirect immunofluorescent straining technique sion initially subsided, but relapse occurred on day
(IFT) and serum neutralization (SN) tests, regardless 251 of treatment [64]. Historically, FIP was regarded
of the mode of inoculation. The SN test revealed an as a progressive, fatal disease; however, with the
Ab titer > 2000 on day 9. However, this threshold was development of new antiviral agents, such as nucle-
not reached in the IFT when most cats succumbed oside analogs and protease inhibitors, there are now
(day 18), although the titers continued to increase. views that FIP might be a treatable disease. It is esti-
Cats that survived had titers comparable to those of mated that some cats may locally transmit the disease
the other cats in the SN and IFT tests. Before inocula- for months or even years [65]. Cats diagnosed with
tion with a virus or cell lysate, the responses of cats to advanced FIP often exhibit compromised immunity
ConA vary from week to week [61]. and high viral counts, and the use of glucocorticoid
Pedersen et al. [62] used several FIPV strains, therapy may intensify this condition. Although these
such as FIPV-UCD1, -UCD2, -UCD-3, and -UCD4. medications are crucial for managing the immune
Cats infected with FIP-UCD2, -UCD3, and -UCD4 response associated with FIP, they may render indi-
were administered 1 mL tissue culture fluid from viduals susceptible to bacterial infections through
Felis catus whole fetus (Fcwf)-4 cells infected with overall immunosuppression and myelosuppression.
the fifth-passage virus. The inoculation route included Therefore, broad-spectrum antibiotics are required
either oronasal (1/2 mL orally and 1/2 mL intranasal) for preventive purposes. Therefore, amoxicillin
or intraperitoneal administration. Additional FIPV and cefadroxil are considered viable alternatives. In
strains were also introduced into infected cats, as cases of confirmed infection, antibiotics should be
previously documented. Cell immunity to FIPV can selected based on culture results and sensitivity tests
be assessed in two ways: (1) by observing distinct [66]. Supportive therapy entails the use of appe-
lymphocyte growth in response to the FIPV antigen tite enhancers (such as mirtazapine, up to 2 mg/cat/
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day), vitamin B12 supplements (administered weekly with antiviral medications, such as tenofovir, ente-
through subcutaneous injection at 0.002 mg/kg or cavir, and ribavirin, it can effectively combat hepa-
orally at 0.25 mg/cat daily), antioxidants, and hydra- titis B and/or C virus infections. However, reliance
tion therapy. The efficacy of effusion drying remains solely on this approach seldom yields success. The
an ongoing topic [65]. third strategy involves non-specific strengthening
The use of therapeutic abdominocentesis remains of the immune system to overcome infection. Some
controversial due to the potential harm caused by the treatments involve the combination of one or more
removal of substantial and rapidly fluctuating fluid therapeutic methods. Irrespective of the chosen
volumes. In some instances, treatment was performed approach, rigorous clinical trials assessing safety and
concurrently with intracavitary steroid administration, efficacy should be conducted for any article in a sci-
specifically dexamethasone at a dose of 1 mg/kg once entific journal that asserts the efficacy of therapies
daily until resolution or for a maximum of 7 days, in for FIP [8].
conjunction with other treatments. Temporary resolu- Antiviral medications are categorized into two
tion of effusion was observed in 6 of 36 cats; however, main types: Those that target the cellular machinery
all cats eventually succumbed to FIP [67]. Ribavirin, of viruses that rely on replication assistance and those
also known as 1-β-D-ribofuranosyl-1H-1,2,4-tri- that focus on specific processes during viral infection
azole-3-carboxamide, is a broad-spectrum triazole and replication. Drugs that target cellular systems tend
nucleoside that is notable for its antiviral activity to be less effective because they can harm both the host
against both FCoV and other RNA and DNA viruses. and the virus. While prednisolone and alkylating med-
Unlike most conventional antiviral drugs, which pri- ications, such as cyclophosphamide, have been used
marily inhibit polymerase, this nucleoside analog to alleviate clinical symptoms in cats with FIP, limited
permits DNA and RNA synthesis but likely interferes evidence supports their efficacy in improving illness
with viral messenger RNA (mRNA) capping, inhib- outcomes. Rather than resorting to less focused treat-
iting viral protein production. Therapeutic doses are ment approaches, efforts have been made to suppress
challenging to produce in vivo due to toxicity, and specific cytokines believed to play crucial roles in FIP
cats are particularly susceptible to adverse effects. development. Tumor necrosis factor inhibitors have
Although ribavirin is active against FCoV in vitro, it been used to alleviate the pain symptoms associated
is ineffective against FIP in cats. Hartman et al. [34] with FIP [69]. The most effective antiviral drugs target
administered ribavirin (16.5 mg/kg orally, intramus- specific segments of the viral genome to control critical
cularly, or intravenously every 24 h for 10–14 days) processes during infection or replication. FCoV shares
to select kittens free of pathogens 18 h after a viral numerous genes with functions analogous to HIV-1,
trial that induced FIP. The FIP killed all of the kit- including RNA virus-dependent polymerases and pro-
tens, including those treated with ribavirin and those teases. Retroviral proteases are vital targets of HIV-1,
left untreated. The clinical signs of illness were more and the combination of reverse transcriptase, protease,
severe in kittens treated with ribavirin, and their aver- and integrase inhibitors has significantly transitioned
age survival time was shorter. Hemolysis is the most HIV-1 into chronic subclinical infections in many
common adverse reaction in cats, as documented patients. Building on the successes of other viral pro-
in a study by Hartman et al. [34] (including those tease inhibitors, similar medications targeting the main
using 11 mg/kg). This phenomenon is attributed to protease (3CL) encoded by coronaviruses and norovi-
the sequestration of medications by red blood cells. ruses are currently under development [8]. Cytokines
In addition, harmful dose-related effects occur in the have been used to modulate immune responses with
bone marrow, particularly affecting megakaryocytes inconsistent results. Recombinant human and feline
(leading to thrombocytopenia and bleeding) and interferon has no significant effect in cats with FIP.
erythroid precursors [34]. Prednisolone is commonly The immunostimulant polyprenyl, which enhances T
used to alleviate symptoms associated with chronic lymphocyte response to induce cell-mediated immu-
inflammation despite the lack of clinical trials sup- nity in cats, has shown mixed success. Its mechanism
porting its use. An initial oral dose of 0.5 mg/kg twice of action, however, remains unclear. Notably, success-
daily is recommended orally. A previous study by ful dry-type FIP has improved the survival of infected
Meli et al. [68] indicated that cats with non-effusive cats. Conversely, this success has not been replicated
FIP had a considerably shorter survival duration than in cats with wet-type FIP. In a field study using this
those treated with corticosteroids or immunostimu- chemical, 8 of 60 cats with FIP survived for more than
lants [65]. Cats with FIP can be treated using vari- 200 days, with 4 exceeding 300 days; all affected cats
ous techniques. Medications that specifically inhibit had dry-type FIP [70].
viral replication have demonstrated efficacy against Prospectively managed care trials involving
various viral conditions, such as human immunodefi- field cats with either confirmed or strongly suggested
ciency virus type 1 (HIV-1), hepatitis B, and hepatitis diagnoses of FIP demonstrated that oral administra-
C viruses. Another approach involves impeding key tion of the nucleoside analog GS-441524, an active
elements of the inflammatory response using drugs, component of the multicomponent drug Mutian®
such as interferons. When interferon-α is combined Xraphconn MT0901 (PATENT US10988503B1),
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significantly reduced viral RNA loads in blood, effu- most pathologies observed in FIP are caused by the
sion, and feces soon after therapy initiation. Notably, response of immune cells to viral infections and the
by day 14, no viremic cats had been observed. These immune system’s reaction to the infected cells. In this
results underscore the high efficacy of the treatment. case, a widespread form of FIP arises because of the
Furthermore, Ab titers consistently decreased through- failure to establish a T-cell defense against a B-cell
out therapy [68]. GS-441524, a 1′-cyano-substituted reaction. Conversely, cats immunized with this dis-
adenine C-nucleoside ribose analog, effectively sup- ease may exhibit a strong cellular immune response to
presses viral RNA synthesis. Importantly, GS-441524 mitigate the harmful effects of Abs [16].
and a previously identified 3C-like antiviral protease An imbalance between T-cell and T-cell immu-
inhibitor have proven effective against FIPV in both nological responses in B lymphocytes is believed
trial settings and cases of spontaneously acquired FIP. to be one reason that cats cannot fight FIPV infec-
However, treating the ocular and CNS manifestations tion. Macrophages overexpress CD40, interleukin 6,
of FIP poses challenges because of limited drug pene- mRNA, and activate factor B cells, all of which have
tration across the blood–brain and blood-eye barriers. previously been linked to high Ab reliance. A previ-
Elevated relapse rates in CNS-related FIP cases have ous study by Malbon et al. [78] has investigated the
been observed with protease inhibitor-based therapies, involvement of T-cell regulatory (Treg) and natu-
whereas GS-441524 shows promise in treating ophthal- ral killer (NK) cells in intrinsic and flexible cellular
mic and neurological manifestations of FIP. The initial immunity in felines treated with natural FIP. Felines
field study using GS-441524 for naturally acquired, with FIP had significantly fewer Tregs and NK cells in
non-neurological FIP used a dose of 2 mg/kg, which their peripheral blood, mesenteric lymph nodes, and
was found to be insufficient for cats with neurologi- spleens, but their mesentery and kidneys were compa-
cal symptoms [46]. GS-441524, the active metabolite rable to those of well-infected and uninfected felines.
of remdesivir (RDV), acts as an RNA chain termina- Healthy cats had more NK cells in their lymph nodes
tor for viral RNA-dependent RNA polymerase and than FIP-fed cats and had decreased toxicity levels. It
strongly inhibits FIPV in both tissue culture and exper- appears that FIPV infection causes substantial NK cell
imental cats. In vitro experiments and cases of sponta- and Treg depletion and impaired NK cell activity. This
neous FIP have also revealed that GS-441524 inhibited may limit the ability of natural defense mechanisms
FIPV replication in cultured Crandell–Rees feline to combat viruses, dampen immunological responses,
kidney (CRFK) cells and naturally infected feline and cause inflammation [78].
peritoneal macrophages at a concentration of 1.0 µM Abs can promote FIPV uptake and multiplica-
while remaining non-toxic to CRFK cells at concentra- tion in macrophages, contributing to type 3 hyper-
tions up to 100 µM. In an in vivo study, cats infected sensitivity vasculitis (a kind of Ab-mediated immune
with FIPV (FIPV strain m3c-2 serotype I) received a response) [16]. In the context of FIP, cats exhibiting
daily subcutaneous injection of GS-441524 at 5.0 or robust cellular immune responses are considered resis-
2.0 mg/kg BW for 2 weeks [71]. tant to the disease, whereas those with predominant
Infection and Immunity
humoral immune responses are susceptible. Given
FIP’s immune-mediated pathology, what is the ratio-
FCoVs infect both domestic and wild felids nale for protective immunity against the virus? The
globally [72]. Most FECV infections are innocuous converse of protective immunity is non-protective.
and remain unnoticed, resulting in moderate diar- However, some forms of immunity appear to exist, as
rhea [4]. Convincing evidence of FECV-induced there are instances (though rare) of events occurring
chronic infections was first reported in the late 1990s. independently, and seropositivity rates in cats signifi-
In this study, naturally ill cats were separated and cantly exceed the incidence of clinical disease. It has
tested for the virus in their excrement. This study been established that immune cells in healthy cats
demonstrated that FECV induces persistent asymp- exhibit a more robust response to FCoV infection than
tomatic infections identical to natural infections [73]. those in cats with FIP [8].
These data demonstrate that FECVs are primarily The Ab-dependent augmentation of viral infec-
linked to the digestive system, yet they can also infect tion occurs when virus-Ab complexes infect monocytes
monocytes, although not as effectively, and thus dis- or macrophages more effectively than viruses alone
seminate throughout the body [74]. through receptor-mediated endocytosis. Most healthy
Primary FECV infection is either asymptomatic cats tested positive for FCOV Abs and never received
or associated with transitory diarrhea, which is mild and FIP. Thus, Ab molecules do not cause FIP and are not
localized in the lower small and large intestines [75]. present, suggesting the presence of FIP [79].
FECV levels appear to be low in blood monocytes
Animal and Public Health Considerations
during the early stages of infection [76]. However, the
body’s immunity is not always robust; when the Abs Kennedy et al. [70] examined FCoV, a positiv-
level in the blood decreases, cats become susceptible istic, single-stranded, enveloped coronavirus RNA
to reinfection [77]. This secondary infection is similar from the genus Alphacoronavirus, which includes
to the primary infection. Moreover, it is believed that infectious (TGEV), canine coronavirus (CCoV), and
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human coronaviruses (NKT-NL63; HCoV-229E). The Pentoxifylline is extensively used in FIP because
COVID-19 viruses causing severe acute respiratory it effectively reduces vasculitis in humans, a crucial
syndrome (SARS), one of the most prevalent diseases, aspect of the etiology of FIP. However, a trial involv-
are part of the genus Betacoronavirus; however, FCoV ing 23 cats with confirmed FIP showed that pentoxi-
does not infect humans. The avirulent and hypervir- fylline had no impact on life duration, quality of life,
ulent FCoV biotypes also recognized as FIPVs and or other FIP-related factors in clinical or laboratory
FECVs, respectively, are included in this group [80]. settings [69]. Coronaviruses have large genomes with
There is a limited association between SARS-CoV numerous potential target genes, highlighting the
and betacoronavirus infectious agents, which can need for safe and effective antiviral medications. It is
infect pets and other animals. Nevertheless, multiple hoped that ongoing research efforts to combat highly
domestic and wild animals have tested positive for lethal coronavirus infections in humans will lead to
SARS-CoV-2, indicating potential human-to-animal the development of such drugs [84]. However, since
transmission [81]. Pets such as canines, cats, tigers, the advent of SARS and near-East MERS, or Middle
lions, and minks have all tested positive for SARS- East respiratory syndrome, interest in coronaviruses
CoV-2 [81]. This methodology was briefly validated as contagious agents has surged. There are similari-
to ensure that the process adapted from human plasma ties between what is known about coronaviruses in
could be replicated in feline serum. Empty cat serum animals and emerging, potentially fatal viruses in
exhibited no analyte retention time signals. The cal- humans. They continually evolve into new hosts,
ibration curve (n = 11 non-zero concentrations) readily combining with closely related species to cre-
demonstrated a linear relationship (r > 0.99) with each ate novel viruses and can also change cell tropism and
concentration maintaining an accuracy of <10% of the pathogenicity within the same host. This phenom-
nominal value. Antiviral substances were evaluated enon, known as Ab-dependent enhancement, poses
in vitro at doses up to 50 μM. N(4)-hydroxycytidine challenges for vaccines used or tested against various
(NHC) doses above 1.5 μM resulted in notable reduc- viruses, including dengue virus, feline immunodefi-
tions in well uptake values in ultrastructure of Felis ciency virus, and HIV-1 [85].
catus whole fetus (Fcwf-4) cell, indicating cell toxic- This difference begins with COVID-19’s attach-
ity. NHC-associated cytotoxicity has been previously ment to ACE2, an ACE receptor, in humans. The pre-
documented. The intravenous RDV dose matched the diction of ACE2 receptor homology between cats and
initial therapeutic dose of 200 mg used to treat patients humans, as well as the discovery of identical feline
with COVID-19 [38]. and canine ACE2 receptors, indicates that SARS-CoV
Before receiving molnupiravir (MPV), the cats infections may also occur in these pets. FCoVs bind
were fasted, which may have contributed to their nau- to receptors other than the ACE2 receptor observed
sea. The first human investigation of MPVs revealed in felines. FCoV type II uses receptor APN within
that food impacts absorption rates. However, treatment cells [86]. Cats were shown to be particularly vul-
exposure in both fasting and fed states was equiva- nerable to SARS in an experimental study that eval-
lent to that of other cell lines, with a CC50 of approxi- uated the sensitivity of various animal species to the
mately 7.5 μM, similar to the utilization in the human virus [87]. The mechanism underlying type I FCoV
cell line. In a manner akin to human observations, infection remains unclear. Lectin on the cell membrane
MPV was rapidly converted from plasma to NHC, (fDC-SIGN) appears to play a role in the entry of both
which is the active metabolite. Further, investigation FCoV types [88]. According to Decaro et al. [77],
into nausea and ptyalism in two of the three oral RDV each of these CoVs originates in the human-animal
groups is necessary. Considerations for adjusting or interface, driven by increasing deforestation, jun-
maintaining doses similar to those used in humans gle encroachment, anthropomorphization of habi-
should be explored to mitigate the adverse effects of tats, and consumption of threatened and endangered
this medication [82]. Numerous treatments have been wildlife [77]. However, the risk of animal-to-human
proposed for FIP management in cats. Studies indicate transmission remains unknown [89].
that various immunophilins actively engage with anti-
Conclusion
biotics through the coronavirus NSP1 of cyclophilin.
Similar to cyclosporine, a reduction in coronavirus FIP is a severe and often fatal cat disease caused
replication has been observed across various genera, by FCoV mutations. While FCoV primarily exists as
including felines, birds, and humans. This underscores the less virulent FECV, the more pathogenic FIPV
the role of the cellular immune stimulant (cyclophilin) represents a distinct biotype with genetic similar-
in the coronavirus replication process. The authors ities to other viruses, including retroviruses. Only a
suggested that non-immunosuppressive cyclosporine minority of cats infected with FCoV develop FIP,
derivatives could act as broad-spectrum inhibitors for but the disease is challenging to diagnose due to its
emerging human coronaviruses and other viral dis- nonspecific clinical signs. Ongoing research into its
eases. Coronaviruses are prevalent among humans pathogenesis, causative agents, epidemiology, and
and livestock worldwide. This drug has a significant immunity is essential for developing effective preven-
inhibitory effect on virus replication [83]. tion and treatment strategies. FIP affects domestic and
Veterinary World, EISSN: 2231-0916 2429
 Available at www.veterinaryworld.org/Vol.17/November-2024/1.pdf

wild felids, particularly those under two years old, and Feline infectious peritonitis: European Advisory Board on
presents in two main forms: effusive (wet) and non-ef- Cat Diseases Guidelines. Viruses, 15(9): 1847.
8. Pedersen, N.C. (2014) An update on feline infectious perito-
fusive (dry). nitis: Diagnostics and therapeutics. Vet. J., 201(2): 133–141.
Although traditionally viewed as untreatable, 9. Lorusso, E., Mari, V., Losurdo, M., Lanave, G., Trotta, A.,
advancements in therapies, such as GS-441524, have Dowgier, G., Colaianni, M.L., Zatelli, A., Elia, G.,
shown promise in reducing viral loads and improving Buonavoglia, D. and Decaro, N. (2019) Discrepancies
between feline coronavirus antibody and nucleic acid detec-
outcomes for FIP patients. Other treatment options, tion in effusions of cats with suspected feline infectious
including immunomodulators and antivirals, are also peritonitis. Res. Vet. Sci., 125: 421–424.
being investigated, though their effectiveness can 10. Vennema, H., Poland, A., Foley, J. and Pedersen, N.C.
vary. More research is necessary to identify optimal (1998) Feline infectious peritonitis viruses arise by muta-
treatment strategies, especially for cases with neuro- tion from endemic feline enteric coronaviruses. Virology,
243(1): 150–157.
logical or ophthalmic involvement. 11. Ouyang, H., Liu, J., Yin, Y., Cao, S., Yan, R., Ren, Y.,
FCoV infections can be asymptomatic or cause mild Zhou, D., Li, Q., Li, J., Liao, X., Ji, W., Du, B., Si, Y.
diarrhea, particularly in domestic cats. A robust immune and Hu, C. (2022) Epidemiology and comparative analy-
response typically helps prevent FIP, whereas a weakened ses of the S Gene on feline coronavirus in central China.
Pathogens, 11(4): 460.
immune system can increase susceptibility to secondary 12. Pedersen, N.C., Johnson, L. and Theilen, G.H. (1984)
infections. Studies suggest the interplay between antibod- Biological behavior of tumors and associated retroviremia
ies and the virus may enhance infection risk. in cats inoculated with Snyder-Theilen fibrosarcoma virus
and the phenomenon of tumor recurrence after primary
Authors’ Contributions regression. Infect. Immun., 43(2): 631–636.
13. Kennedy, M., Boedeker, N., Gibbs, P. and Kania, S. (2001)
TIS, QADA, RAD, DAFS, GNR, VAH, Deletions in the 7a ORF of feline coronavirus associ-
and GPS: Conceptualized the study, collected the ated with an epidemic of feline infectious peritonitis. Vet.
literature, and drafted and edited the manuscript. All Microbiol., 81(3): 227–234.
authors have read and approved the final manuscript. 14. Lin, C.N., Su, B.L., Huang, H.P., Lee, J.J., Hsieh, M.W.
and Chueh, L.L. (2009) Field strain feline coronaviruses
Acknowledgments with small deletions in ORF7b associated with both enteric
infection and feline infectious peritonitis. J. Feline Med.
The authors are thankful to Universitas Airlangga Surg., 11(6): 413–419.
for providing the necessary facilities for this study. 15. Takano, Y., Yamada, S., Doki, T., and Hohdatsu, T. (2019).
The authors did not receive any funds for this study. Pathogenesis of oral type I feline infectious peritonitis virus
(FIPV) infection: Antibody-dependent enhancement infec-
Competing Interests tion of cats with type I FIPV via the oral route. J. Vet. Med.
Sci., 81(6), 911-915.
The authors declare that they have no competing 16. Pedersen, N.C. (2009) A review of feline infectious peri-
interests. tonitis virus infection: 1963–2008. J. Feline Med. Surg.,
11(4): 225–258.
Publisher’s Note 17. Chappuis, G., Duret, C. (1978) Feline infectious peritoni-
Veterinary World remains neutral with regard to tis: Present knowledge. Comp. Immunol. Microbiol. Infect.
Dis., 1(1–2): 115–120.
jurisdictional claims in published institutional affiliation. 18. Moyadee, W., Sunpongsri, S., Choowongkomon, K.,
References Roytrakul, S., Rattanasrisomporn, A., Tansakul, N. and
Rattanasrisomporn, J. (2024) Feline infectious peritonitis:
1. Thayer, V., Gogolski, S., Felten, S., Hartmann, K., A comprehensive evaluation of clinical manifestations, lab-
Kennedy, M. and Olah, G.A. (2022) 2022 AAFP/EveryCat oratory diagnosis, and therapeutic approaches. J. Adv. Vet.
Feline infectious peritonitis diagnosis guidelines. J. Feline Anim. Res., 11(1): 19–26.
Med. Surg. 24(9): 905–933. 19. Martínez, J., Reinacher, M., Perpiñán, D. and Ramis, A.
2. Si, F., Yu, R., Dong, S., Chen, B., Li, C. and Song, S. (2024) (2008) Identification of group 1 coronavirus antigen in mul-
Towards a safer future: Enhancing vaccine development to tisystemic granulomatous lesions in ferrets (Mustela puto-
combat animal coronaviruses. Vaccines (Basel), 12(3): 1–31. rius furo). J. Comp. Pathol., 138(1): 54–58.
3. Olsen, C.W. (1993) A review of feline infectious peritoni- 20. Boghian, V. (2023) Morphoclinical and paraclinical fea-
tis virus: Molecular biology, immunopathogenesis, clinical tures of feline infectious peritonitis (FIP). J. Appl. Life Sci.,
aspects, and vaccination. Vet. Microbiol., 36(1–2): 1–37. 56(1(193)): 115–126.
4. Tekes, G. and Thiel, H.J. (2016) Feline coronaviruses: 21. Yin, Y., Li, T., Wang, C., Liu, X., Ouyang, H., Ji, W., Liu, J.,
Pathogenesis of feline infectious peritonitis. Adv. Virus Res., Liao, X., Li, J. and Hu, C. (2021) A retrospective study of
96: 193–218. clinical and laboratory features and treatment on cats highly
5. Xia, H., Li, X., Zhao, W., Jia, S., Zhang, X., Irwin, D.M. suspected of feline infectious peritonitis in Wuhan, China.
and Zhang, S. (2020) Adaptive evolution of feline corona- Sci. Rep., 11(1): 5208.
virus genes based on selection analysis. Biomed. Res. Int., 22. Paltrinieri, S., Giordano, A., Stranieri, A., Lauzi, S. (2021)
2020: 9089768. Feline infectious peritonitis (FIP) and coronavirus disease
6. Poland, A.M., Vennema, H., Foley, J.E. and Pedersen, N.C. 19 (COVID‐19): Are they similar? Transbound. Emerg.
(1996) Two related strains of feline infectious peritonitis virus Dis., 68(4): 1786–1799.
isolated from immunocompromised cats infected with a feline 23. Crawford, A.H., Stoll, A.L., Sanchez-Masian, D.,
enteric coronavirus. J. Clin. Microbiol., 34(12): 3180–3184. Shea,A., Michaels, J., Fraser, A.R. and Beltran, E. (2017)
7. Tasker, S., Addie, D.D., Egberink, H., Hofmann- Clinicopathologic features and magnetic resonance imag-
Lehmann, R., Hosie, M.J., Truyen, U., Belák, S., ing findings in 24 cats with histopathologically confirmed
Boucraut-Baralon, C., Frymus, T., Lloret, A., Marsilio, F., neurologic feline infectious peritonitis. J. Vet. Intern. Med.,
Pennisi, M.G., Thiry, E., Möstl, K. and Hartmann, K. (2023) 31(5): 1477–1486.
Veterinary World, EISSN: 2231-0916 2430
 Available at www.veterinaryworld.org/Vol.17/November-2024/1.pdf

24. Kornegay, J.N. (19patho8) Feline infectious peritonitis: The peritonitis. J. Vet. Diagn. Invest., 30(3): 392–399.
central nervous system form. J. Am. Anim. Hosp. Assoc., 44. Guan, X., Li, H., Han, M., Jia, S., Feng, B., Gao, X.,
14(5): 580–584. Wang, Z., Jiang, Y., Cui, W., Wang, L. and Xu, Y. (2020).
25. Kipar, A. and Meli, M.L. (2014) Feline infectious peritoni- Epidemiological investigation of feline infectious peritoni-
tis: Still an enigma? Vet. Pathol., 51(2): 505–526. tis in cats living in Harbin, Northeast China from 2017 to
26. Giori, L., Giordano, A., Giudice, C., Grieco, V. and 2019 using a combination of an EvaGreen-based real-time
Paltrinieri, S. (2011) Performances of different diagnostic RT-PCR and serum chemistry assays. Mol. Cell. Probes,
tests for feline infectious peritonitis in challenging clinical 49: 101495.
cases. J. Small Anim. Pract., 52(3): 152–157. 45. Martinez, M.L., Weiss, R.C. (1993) Detection of feline
27. Sweet, A.N., André, N.M., Stout, A.E., Licitra, B.N. and infectious peritonitis virus infection in cell cultures and
Whittaker, G.R. (2022) Clinical and molecular relationships peripheral blood mononuclear leukocytes of experimen-
between COVID-19 and feline infectious peritonitis (FIP). tally infected cats using a biotinylated cDNA probe. Vet.
Viruses, 14(3): 481. Microbiol., 34(3): 259–271.
28. Slaviero, M., Cony, F.G., da Silva, R.C., De Lorenzo, C., de 46. Dickinson, P.J., Bannasch, M., Thomasy, S.M.,
Almeida, B.A., Bertolini, M., Driemeier, D., Pavarini, S.P. Murthy, V.D., Vernau, K.M., Liepnieks, M., Montgomery, E.,
and Sonne, L. (2024) Pathological findings and patterns of Knickelbein, K.E., Murphy, B. and Pedersen, N.C. (2020)
feline infectious peritonitis in the respiratory tract of cats. J. Antiviral treatment using the adenosine nucleoside ana-
Comp. Pathol., 210: 15–24. logue GS −441524 in cats with clinically diagnosed neu-
29. Andrew, S. E. (2000). Feline infectious peritonitis. Vet. rological feline infectious peritonitis. J. Vet. Intern. Med.,
Clin. North Am. Small Anim. Pract., 30(5): 987–1000. 34(3): 1587–1593.
30. Berg, A.L., Ekman, K., Belák, S. and Berg, M. (2005) 47. Djani, D.M. and Thomas, W.B. (2019) What is your neuro-
Cellular composition and interferon-γ expression of the logic diagnosis? J. Am. Vet. Med. Assoc., 254(5): 587–589.
local inflammatory response in feline infectious peritonitis 48. Müller, T.R., Penninck, D.G., Webster, C.R.L. and
(FIP). Vet. Microbiol., 111(1–2): 15–23. Conrado, F.O. (2023) Abdominal ultrasonographic find-
31. Evermann, J.F., McKeirnan, A.J. and Ott, R.L. (1991) ings of cats with feline infectious peritonitis: An update. J.
Perspectives on the epizootiology of feline enteric corona- Feline Med. Surg., 25(12).
virus and the pathogenesis of feline infectious peritonitis. 49. Aydin, H. and Yildirim, S. (2019) Investigation of the rela-
Vet. Microbiol., 28(3): 243–255. tion between feline infectious peritonitis and retroviruses in
32. Anwer, A.Z., Mousa, M.R., Halium, M.A., Abouelela, Y.S. cats. GSC Biol. Pharm. Sci., 6(2): 71–78.
and Elsaid, H.M. (2022) Clinical and pathological studies 50. Schmidt, M. and Ondreka, N. (2019) Hydrocephalus in
on feline infectious peritonitis in Egypt. Int. J. Vet. Sci., animals. In: Pediatric Hydrocephalus. 2nd ed. Springer
11(2): 159–167. International Publishing, Berlin, p53–95.
33. Yuya, N., Hideo, M., Takehisa, S., Takashi, U., Satoru, M., 51. Park, S., Bae, Y. and Choi, J. (2015) Pleuropneumonia in
Tsuyosi, O.(2013). Dysuria Similar to Urethral Atresia in a cat with feline infectious peritonitis. J. Vet. Clin., 32(5):
central nervous system-type of feline infectious peritonitis/ 454–458.
Type 1 Feline Coronaviruses. J Stage, 66(2): 126-130. 52. Dunbar, D., Kwok, W., Graham, E., Armitage, A., Irvine, R.,
34. Hartmann, K. (2005) Feline infectious peritonitis. Vet. Clin. Johnston, P., McDonald, M., Montgomery, D., Nicolson, L.,
Small Anim. Pract., 35(1): 39–79. Robertson, E., Weir, W. and Addie, D.D. (2019) Diagnosis
35. Brown, M.A., Troyer, J.L., Pecon-Slattery, J., Roelke, M.E. of non-effusive feline infectious peritonitis by reverse tran-
and O’Brien, S.J. (2009) Genetics and pathogenesis of scriptase quantitative PCR from mesenteric lymph node
feline infectious peritonitis virus. Emerg. Infect. Dis., 15(9): fine-needle aspirates. J. Feline Med. Surg., 21(10): 910–921.
1445–1452. 53. Doenges, S.J., Weber, K., Dorsch, R., Fux, R., Fischer, A.,
36. De Groot-Mijnes, J.D.F., van Dun, J.M., van der Most, R.G. Matiasek, L.A., Matiasek, K. and Hartmann, K. (2016)
and de Groot, R.J. (2005) Natural history of a recurrent Detection of feline coronavirus in cerebrospinal fluid for
feline coronavirus infection and the role of cellular immu- diagnosis of feline infectious peritonitis in cats with and with-
nity in survival and disease. J. Virol., 79(2): 1036–1044. out neurological signs. J. Feline Med. Surg., 18(2): 104–109.
37. Chang, H.W., Egberink, H.F., Halpin, R., Spiro, D.J. and 54. Li, X. and Scott, F.W. (1994) Detection of feline corona-
Rottier, P.J.M. (2012) Spike protein fusion peptide and feline viruses in cell cultures and in fresh and fixed feline tissues
coronavirus virulence. Emerg. Infect. Dis., 18(7): 1089–1095. using polymerase chain reaction. Vet. Microbiol., 42(1):
38. Cook, S., Wittenburg, L., Yan, V.C., Theil, J.H., Castillo, D., 65–77.
Reagan, K.L., Williams, S., Pham, C.D., Li, C., Muller, F.L. 55. Haake, C., Cook, S., Pusterla, N. and Murphy, B. (2020)
and Murphy, B.G. (2022) An optimized bioassay for screen- Coronavirus infections in companion animals: Virology,
ing combined anticoronaviral compounds for efficacy epidemiology, clinical and pathologic features. Viruses,
against feline infectious peritonitis virus with pharmacoki- 12(9): 1023.
netic analyses of GS-441524, remdesivir, and molnupiravir 56. Sevinç, M., Ok, M. and Baş, T.M. (2020) Coronavirus
in cats. Viruses, 14(11): 2429. infection in cats, Eurasian Journal of Veterinary Sciences,
39. Takano, T., Wakayama, Y. and Doki, T. (2019) Endocytic path- 56(1), pp. 106–117.
way of feline coronavirus for cell entry: Differences in sero- 57. Murphy, B.G., Castillo, D., Neely, N.E., Kol, A., Brostoff, T.,
type-dependent viral entry pathway. Pathogens, 8(4): 300. Grant, C.K. and Reagan, K.L. (2024) Serologic, virologic
40. Gao, Y.Y., Wang, Q., Liang, X.Y., Zhang, S., Bao, D., and pathologic features of cats with naturally occurring
Zhao, H., Li, S.B., Wang, K., Hu, G.X. and Gao, F.S. feline infectious peritonitis enrolled in antiviral clinical tri-
(2023). An updated review of feline coronavirus: Mind the als. Viruses, 16(3): 462.
two biotypes. Virus Res., 326: 199059. 58. Hayashi, T., Utsumi, F., Takahashi, R. and Fujiwara, K.
41. Moyadee, W., Jaroensong, T., Roytrakul, S., Boonkaewwan, C. (1980) Pathology of non-effusive type feline infectious
and Rattanasrisomporn, J. (2019) Characteristic clinical signs peritonitis and experimental transmission. Nihon Juigaku
and blood parameters in cats with feline infectious peritonitis. Zasshi, 42(2): 197–210.
Agric. Nat. Resour., 55(4): 209–212. 59. Tasker, S. (2018) Diagnosis of feline infectious peritonitis:
42. Felten, S. and Hartmann, K. (2019) Diagnosis of feline Update on evidence supporting available tests. J. Feline
infectious peritonitis: A review of the current literature. Med. Surg., 20(3): 228–243.
Viruses, 11(11): 1068. 60. Hohdatsu, T., Okada, S. and Koyama, H. (1991)
43. Rissi, D.R. (2018) A retrospective study of the neuropathol- Characterization of monoclonal antibodies against feline
ogy and diagnosis of naturally occurring feline infectious infectious peritonitis virus type II and antigenic relationship

Veterinary World, EISSN: 2231-0916 2431

 Available at www.veterinaryworld.org/Vol.17/November-2024/1.pdf

between feline, porcine, and canine coronaviruses. Arch. response: A whole-transcriptome analysis of the mesenteric
Virol., 117(1–2): 85–95. lymph nodes in cats with and without feline infectious peri-
61. Stoddart, M.E., Gaskell, R.M., Harbour, D.A. and tonitis. Pathogens, 9(7): 524.
Gaskell, C.J. (1988) Virus shedding and immune responses 79. Hartmann, K., Binder, C., Hirschberger, J., Cole, D.,
in cats inoculated with cell culture-adapted feline infectious Reinacher, M., Schroo, S., Frost, J., Egberink, H., Lutz, H.
peritonitis virus. Vet. Microbiol., 16(2): 145–158. and Hermanns, W. (2003) Comparison of different tests to
62. Pedersen, N.C. (1987) Virologic and immunologic aspects diagnose feline infectious peritonitis. J. Vet. Intern. Med.,
of feline infectious peritonitis virus infection. Adv. Exp. 17(6): 781–790.
Med. Biol., 218: 529–550. 80. Addie, D., Houe, L., Maitland, K., Passantino, G. and
63. Berliner, E.A. (2021) Feline coronavirus and feline infec- Decaro, N. (2020) Effect of cat litters on feline coronavi-
tious peritonitis. In: Infectious Disease Management in rus infection of cell culture and cats. J. Feline Med. Surg.,
Animal Shelters. Wiley, United States, p367–392. 22(4): 350–357.
64. Delaplace, M., Huet, H., Gambino, A. and Le Poder, S. (2021) 81. Halfmann, P.J., Hatta, M., Chiba, S., Maemura, T., Fan, S.,
Feline coronavirus antivirals: A review. Pathogens, 10(9): 1150. Takeda, M., Kinoshita, N., Hattori, S.I., Sakai-Tagawa, Y.,
65. Barker, E.N. and Tasker, S. (2020) Advances in molecular Iwatsuki-Horimoto, K., Imai, M. and Kawaoka, Y. (2020)
diagnostics and treatment of feline infectious peritonitis. Transmission of SARS-CoV-2 in domestic cats. N. Engl. J.
Adv. Small Anim. Care, 1: 161–188. Med., 383(6): 592–594.
66. Berry, M.L. (2001) Feline infectious peritonitis. In: Feline 82. Beigel, J.H., Tomashek, K.M., Dodd, L.E., Mehta, A.K.,
Internal Medicine Secrets. Elsevier Health Sciences, Zingman, B.S., Kalil, A.C., Hohmann, E., Chu, H.Y.,
Netherlands, p175. Luetkemeyer, A., Kline, S., Lopez de Castilla, D.,
67. Meli, M.L., Spiri, A.M., Zwicklbauer, K., Krentz, D., Finberg, R.W., Dierberg, K., Tapson, V., Hsieh, L.,
Felten, S., Bergmann, M., Dorsch, R., Matiasek, K., Patterson, T.F., Paredes, R., Sweeney, D.A., Short, W.R.,
Alberer, M., Kolberg, L., von Both, U., Hartmann, K. and Touloumi, G., Lye, D.C., Ohmagari, N., Oh, M.-D.,
Hofmann-Lehmann, R. (2022) Fecal feline coronavirus RNA Ruiz-Palacios, G.M., Benfield, T., Fätkenheuer, G.,
shedding and spike gene mutations in cats with feline infec- Kortepeter, M.G., Atmar, R.L., Creech, C.B., Lundgren, J.,
tious peritonitis treated with GS-441524. Viruses, 14(5): 1069. Babiker, A.G., Pett, S., Neaton, J.D., Burgess, T.H.,
68. Khoo, C.K., Dahlan, R., Mat Desa, Z.M., Syarina, P.N.A., Bonnett, T., Green, M., Makowski, M., Osinusi, A.,
Salim, S.S.H., Barker, Z., Abu Hassan, M.H.A., Hassan, R. Nayak, S., Lane, H.C. and ACTT-1 Study Group Members.
and Mohd Saeid, F.H.M. (2022) Molecular detection of (2020) Remdesivir for the treatment of Covid-19 - final
lumpy skin disease virus in Malaysia 2021. Int. J. Infect. report. N. Engl. J. Med., 383(19): 1813–1826.
Dis., 116: S1–S130. 83. Pfefferle, S., Schöpf, J., Kögl, M., Friedel, C.C.,
69. Fischer, Y., Ritz, S., Weber, K., Sauter‐Louis, C. and Müller, M.A., Carbajo-Lozoya, J., Stellberger, T., von
Hartmann, K. (2011) Randomized, placebo controlled study Dall’Armi, E., Herzog, P., Kallies, S., Niemeyer, D., Ditt, V.,
of the effect of propentofylline on survival time and quality Kuri, T., Züst, R., Pumpor, K., Hilgenfeld, R., Schwarz, F.,
of life of cats with feline infectious peritonitis. J. Vet. Intern. Zimmer, R., Steffen, I., Weber, F., Thiel, V., Herrler, G.,
Med., 25(6): 1270–1276. Thiel, H.J., Schwegmann-Wessels, C., Pöhlmann, S.,
70. Kennedy, M.A. (2020) Feline infectious peritonitis: Update Haas, J., Drosten, C. and von Brunn, A. (2011) The SARS-
on pathogenesis, diagnostics, and treatment. Vet. Clin. coronavirus-host interactome: Identification of cyclophilins
North Am. Small Anim. Pract., 50(5): 1001–1011. as target for pan-coronavirus inhibitors. PLOS Pathog.,
71. Izes, A.M., Yu, J., Norris, J.M. and Govendir, M. (2020) 7(10): e1002331.
Current status on treatment options for feline infectious 84. Zhang, X., Chu, H., Wen, L., Shuai, H., Yang, D., Wang, Y.,
peritonitis and SARS-CoV-2 positive cats. Vet. Q., 40(1): Hou, Y., Zhu, Z., Yuan, S., Yin, F., Chan, J.F.W. and
322–330. Yuen, K.Y. (2020) Competing endogenous RNA network
72. Wasieri, J., Schmiedeknecht, G., Förster, C., König, M. and profiling reveals novel host dependency factors required
Reinacher, M. (2009) Parvovirus infection in a Eurasian for MERS-CoV propagation. Emerg. Microbes Infect., 9(1):
lynx (Lynx lynx) and in a European wildcat (Felis silvestris 733–746.
silvestris). J. Comp. Pathol., 140(2–3): 203–207. 85. Sharun, K., Sircar, S., Malik, Y.S., Singh, R.K. and
73. Tang, Y.W., Procop, G.W. and Persing, D.H. (1997) Dhama, K. (2020) How close is SARS-CoV-2 to canine
Molecular diagnostics of infectious diseases. Clin. Chem., and feline coronaviruses? J. Small Anim. Pract., 61(8):
43(11): 2021–2038. 523–526.
74. Lewis, C.S., Porter, E., Matthews, D., Kipar, A., Tasker, S., 86. Guo, H., Guo, A., Wang, C., Yan, B., Lu, H. and Chen, H.
Helps, C.R. and Siddell, S.G. (2015) Genotyping coronavi- (2008) Expression of feline angiotensin converting enzyme
ruses associated with feline infectious peritonitis. J. Gen. 2 and its interaction with SARS-CoV S1 protein. Res. Vet.
Virol., 96(6): 1358–1368. Sci., 84(3): 494–496.
75. Vogel, L., Van der Lubben, M., Te Lintelo, E.G., 87. Shi, J., Wen, Z., Zhong, G., Yang, H., Wang, C., Huang, B.,
Bekker, C.P.J., Geerts, T., Schuijff, L.S., Grinwis, G.C.M., Liu, R., He, X., Shuai, L., Sun, Z., Zhao, Y., Liu, P.,
Egberink, H.F. and Rottier, P.J.M. (2010) Pathogenic char- Liang, L., Cui, P., Wang, J., Zhang, X., Guan, Y., Tan, W.,
acteristics of persistent feline enteric coronavirus infection Wu, G., Chen, H., Bu, Z. and Bu, Z. (2020) Susceptibility
in cats. Vet. Res., 41(5): 71. of ferrets, cats, dogs, and other domesticated animals to
76. Kipar, A., Meli, M.L., Baptiste, K.E., Bowker, L.J. and SARS-coronavirus 2. Science, 368(6494): 1016–1020.
Lutz, H. (2010) Sites of feline coronavirus persistence in 88. Van Hamme, E., Desmarets, L., Dewerchin, H.L. and
healthy cats. J. Gen. Virol., 91(7): 1698–1707. Nauwynck, H.J. (2011) Intriguing interplay between feline
77. Decaro, N., Martella, V., Saif, L.J. and Buonavoglia, C. infectious peritonitis virus and its receptors during entry in
(2020) COVID-19 from veterinary medicine and one health primary feline monocytes. Virus Res., 160(1–2): 32–39.
perspectives: What animal coronaviruses have taught us. 89. Sit, T.H.C., Brackman, C.J., Ip, S.M., Tam, K.W.S.,
Res. Vet. Sci., 131: 21–23. Law, P.Y.T., To, E.M.W., Yu, V.Y.T., Sims, L.D.,
78. Malbon, A.J., Russo, G., Burgener, C., Barker, E.N., Tsang, D.N.C., Chu, D.K.W., Perera, R.A.P.M., Poon,
Meli, M.L., Tasker, S. and Kipar, A. (2020) The effect of L.L.M. and Peiris, M. (2020) Infection of dogs with SARS-
natural feline coronavirus infection on the host immune CoV-2. Nature, 586(7831): 776–778.

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