MINI REVIEW

published: 20 March 2020

doi: 10.3389/fpubh.2020.00083

Influenza A Virus Infection in Cats

and Dogs: A Literature Review in the
Light of the “One Health” Concept
Stéphanie Borland 1 , Patrice Gracieux 1 , Matthew Jones 2 , François Mallet 3 and
Javier Yugueros-Marcos 1*
1
bioMérieux S.A./BioFire Diagnostics LLC Research and Development, Centre Christophe Mérieux, Grenoble, France,
2
BioFire Diagnostics LLC, Salt Lake City, UT, United States, 3 Joint Research Unit, Hospice Civils de Lyon, bioMérieux S.A.,
Centre Hospitalier Lyon Sud, Pierre-Benite, France

Influenza A viruses are amongst the most challenging viruses that threaten both human
and animal health. Constantly evolving and crossing species barrier, the emergence of
novel zoonotic pathogens is one of the greatest challenges to global health security.
During the last decade, considerable attention has been paid to influenza virus infections
in dogs, as two canine H3N8 and H3N2 subtypes caused several outbreaks through
the United States and Southern Asia, becoming endemic. Cats, even though less
Edited by: documented in the literature, still appear to be susceptible to many avian influenza
Mirella Salvatore,
Cornell University, United States infections. While influenza epidemics pose a threat to canine and feline health, the
Reviewed by: risks to humans are largely unknown. Here, we review most recent knowledge of the
Luis Martinez-Sobrido, epidemiology of influenza A viruses in dogs and cats, existing evidences for the abilities
University of Rochester, United States
of these species to host, sustain intraspecific transmission, and generate novel flu A
Colin Parrish,
Cornell University, United States lineages through genomic reassortment. Such enhanced understanding suggests a need
*Correspondence: to reinforce surveillance of the role played by companion animals-human interface, in light
Javier Yugueros-Marcos of the “One Health” concept and the potential emergence of novel zoonotic viruses.
javier.yuguerosmarcos@
biomerieux.com Keywords: influenza, one health, zoonosis, dog, cat, interspecies transmission, public health

Specialty section:
This article was submitted to INTRODUCTION
Infectious Diseases - Surveillance,
Prevention and Treatment, Influenza is an acute infectious respiratory disease caused, in humans, by influenza type A or type
a section of the journal B viruses. While the latter type circulates only among humans, influenza A viruses (IAV) can also
Frontiers in Public Health
be isolated from a wide variety of animal species. Wild migratory birds and bats are main natural
Received: 18 December 2019 reservoirs, from where virus uses to spill over into other animal hosts like ducks, chickens, horses,
Accepted: 02 March 2020 pigs, whales, cats, dogs, etc. IAVs viruses commonly exhibit restricted host range, but occasionally
Published: 20 March 2020
transmit from one species to another host (1). Notably, numerous spillover events arose primarily
Citation: from poultry and swine that pose a significant threat to human health as historically, most human
Borland S, Gracieux P, Jones M,
pandemics have emerged from avian and swine hosts (2, 3). In a world where the number of cat and
Mallet F and Yugueros-Marcos J
(2020) Influenza A Virus Infection in
dog owners is increasing, and social behavior tends to enroll these animal species as family members
Cats and Dogs: A Literature Review in (4–6), this review aims at providing an up-to-date picture of the epidemiology of IAV in dogs and
the Light of the “One Health” Concept. cats and their transmission modes. Their evolution and the consequences of genetic reassortments
Front. Public Health 8:83. of IAV are further discussed, leading us to provide recommendations on surveillance tools and on
doi: 10.3389/fpubh.2020.00083 the role that diagnostic tools could play in the “One Health” concept approach.

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Borland et al. Influenza A Virus in Dogs and Cats

EPIDEMIOLOGY OF IAV IN CATS AND animals live in dense population (46–50). Noteworthy, no CIV-
DOGS H3N8 infection has been reported since 2016.
Around 2006, a novel H3N2 subtype arose in dogs in China
Currently, five subtypes of IAV are frequently described in the and South Korea, and then rapidly spread into several areas of
literature as cause of acute respiratory illness in cats and dogs: Southeast Asia, where it is now stably circulating in the canine
H3N8, H3N2, low pathogenic avian influenza virus (LPAIV) population becoming endemic (and thus referred to as CIV-
H7N2, high pathogenic avian influenza virus (HPAIV) H5N1 as H3N2) (10–12, 51). CIV-H3N2 was first identified in the US
well as the pandemic H1N1 virus, circulating nowadays as the in 2015, as a causative agent of epidemic outbreaks of severe
seasonal flu virus in humans (Table 1). Other subtypes, mainly respiratory disease that affected more than 1,000 dogs in Chicago
from avian origin, or a result of genetic reassortments following and nearby areas (13, 52, 53). Its spread within the US and
co-infections of different avian, swine and human IAV, have Canada may have arisen from rehoming of dogs rescued from
also been isolated from cats and dogs with respiratory disease meat markets imported from Asia to US (14). Despite local
(i.e., H5N6, H5N2, H3N1) (Figure 1). Reports of infection with control measures, the virus has continued circulating among the
human influenza A seasonal types have been published, but to a canine population and has spread to several other areas of the
much lesser extent, not being covered by this review. country, indicating sustained dog-to-dog transmission in the US,
Canine influenza virus (CIV) H3N8 subtype was reported through combinations of multiple incursions into the US from
in 2004 in an outbreak of severe respiratory disease in racing Asia and a series of localized outbreaks and fade-outs (13, 53).
greyhounds, although serological evidence suggested it emerged Some interspecies transmission events to cats have also been
around 1999 (7, 38, 39). The virus has since been considered reported, being further described in section Influenza A Virus
endemic in the canine population in the US, affecting both Interspecies Transmission to Cats and Dogs of this article (15).
racing greyhounds and pets (38). Affected dogs exhibited A LPAIV of the H7N2 subtype, which circulated in live
various degrees of pneumonia and CIV-H3N8 spread readily poultry markets in the eastern and northeastern US during 1994–
from infected dogs to other susceptible dogs through direct 2006, was identified as the causative source of an outbreak in a
contact (40). Other spillover CIV-H3N8 infections have been cat shelter in New York City in December 2016, subsequently
sporadically reported in other parts of the world, such as in spreading to multiple shelters in the states of New York
Canada, UK, Australia, China and Nigeria (41), but no evidence and Pennsylvania. Infected cats experienced clinical signs of
of continuing circulation of CIV-H3N8 has been reported in coughing, sneezing, and runny nose from which they fully
these areas, and the risk of emergence appears very low (8, 41– recovered (17). Under experimental conditions, feline H7N2
45). The CIV-H3N8 subtype appeared to have been primarily subtype was found to replicate efficiently in cat upper and lower
maintained in large urban animal shelters, where susceptible respiratory tracts and had the ability to transmit among cats,

TABLE 1 | Overview of major natural influenza A subtype infections and reassortment events reported in dogs and cats.

Influenza A First isolation Host species Currently reported Severity of Intraspecies Transmission to References
subtypea (localization and (origin) geographic the diseasec transmissibilityd humanse
year) distributionb

CIV-H3N8 Florida, USA, 2004 Dogs (Horse) USAb , UK, Canada + + Never reported (7–9)
CIV-H3N2 China, 2006 Dogs and Cats Southeast Asiab , ++ ++ Never reported (10–16)
(Avian) North Americab
LPAIV H7N2 New York City, USA, Cats (Avian) USA + + Reported once (17, 18)
2016
HPAIV H5N1 Thailand, 2006 Dogs and Cats Thailand, China, +++ –/+ Never reported (19–25)
(Avian) Austria, Germany
A(H1N1)pdm09 Italy, 2009 Dogs and Cats USA, China, Mexico, +++ + Reverse zoonosis (26–34)
(Human) Italy
CIV-H3N1* South Korea, 2010 Dogs (Human) Unknown - - Never reported (35)
CIV-H3N2* South Korea, 2012 Dogs (Human) Unknown ++ + Never reported (36)
CIV-H1N1r* China, 2015 Dogs (Swine) China ++ Unknown Never reported (37)
CIV-H1N2r* China, 2014 Dogs (Swine) China + Unknown Never reported (37)
CIV-H3N2r* China, 2015 Dogs (Swine) China + Unknown Never reported (37)

a CIV, Canine Influenza Virus; HPAIV, High Pathogenic Avian Influenza Virus; pdm, pandemic; LPAIV, Low Pathogenic Avian Influenza Virus; r, reassortant and further highlighted by
an asterisk.
b Refers to endemic subtype in canine population.
c Severity was defined based one the following criteria: + mild respiratory symptoms; ++ severe respiratory symptoms; + + + systemic infection.
d Intraspecies transmissibilty refers to dog-to-dog and cat-to-cat transmission events and was classified as follows: - no evidence of case-to-case transmission; –/+ limited transmission;

++ efficient spreading.
e Reverse Zoonosis refers to an influenza subtype that can be transmitted from humans to companion animals.

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Borland et al. Influenza A Virus in Dogs and Cats

FIGURE 1 | Dogs and cats as mixing vessels for influenza A virus. In green and light blue boxes are represented the genomic structure of reassortants that have been
reported in dogs and cats, respectively. The host origin of the eight segments of viral RNA are displayed as follows: in gray, human; orange, avian; purple, swine;
green, canine. Solid arrows indicate well-described interspecies events, circle arrows indicate gene reassortment events and dashed arrows represent the potential for
those novel viral combinations to jump to humans, although no such case has been reported so far. See text for further details.

indicating adaptation of this avian H7N2 to felines. During the were also reported in domestic cats exhibiting clinical signs of
outbreak, a veterinarian who treated the animals also became acute respiratory infection (27–29, 59, 60). In the latter cases,
infected with feline H7N2 influenza virus and experienced the most likely source of infection was found to be people
respiratory symptoms (17). In addition, another case of cat- in the household. Indeed, as owners of infected cats also had
to-human transmission was reported in an animal shelter a history of severe respiratory disease, with prior infection
employee who experienced mild illness symptoms and who had with A(H1N1)pdm09 virus confirmed (59) or coinciding with
direct exposure to ill cats. No evidence of human-to-human periods of increased influenza activity (28). More, seroprevalence
transmission has been reported so far (54, 55). of antibodies against A(H1N1)pdm09 was three times more
HPAIV H5N1 subtype initially originated in China in 1996 prevalent in pet cats than free-roaming cats (61). In dogs, some
and it has spread since then into many areas in the world, rare cases of natural A(H1N1)pdm09 infections have also been
causing infections in birds of many species (56). Dogs and documented so far (30), notwithstanding the ability of the virus
cats have been infected by direct contact with affected birds, to replicate in dogs respiratory tract in an experimental setting,
especially by eating raw poultry (19–21). Of particular concern, even though symptoms were very mild, and appeared to rather
severe symptoms, not limited to respiratory organs but also transmit inefficiently from dog-to-dog (30).
hepatic and gastrointestinal were reported, and in many cases
systemic infection was evidenced. Subclinical infection of cats
with H5N1 was also reported after contact with infected birds INFLUENZA A VIRUS INTERSPECIES
or their excrement (22), thus indicating that cats may serve TRANSMISSION TO CATS AND DOGS
as a potential asymptomatic H5N1 reservoir. Nevertheless, low
prevalence of H5N1 antibodies was reported in cats sera, even Successful interspecies transmission of IAV is dependent on both
in areas in which birds infected with HPAIV H5N1 had been host and virus genetic factors, and subsequent spread within the
documented (23, 57, 58). new host population requires a period of adaptation of the virus
In Italy, 2009, a pandemic H1N1 [A(H1N1)pdm09] outbreak to the new host (1, 62). Critical host and viral determinants
occurred in a colony of 90 caged stray cats (26). Half of involved in virus specificity and further mechanisms in the
the animal colony had signs of severe acute respiratory and adaptation to cats and dogs are described.
gastrointestinal infections. Serum samples and pharyngeal swabs
were collected from 38 of the 65 surviving cats, and more than Avian Interspecies Transmission
half (55%) of the tested cats were seropositive for the presence Among those determinants in the specificity of IAV for a host,
of A(H1N1)pdm09 antibodies and two swabs were positive for we would highlight the presence of virus receptors on susceptible
the presence of A(H1N1)pdm09 by PCR, highlighting cat-to- host cells, especially those to which the viral hemagglutinin (HA)
cat transmission of the virus (26). Furthermore, several sporadic is able to bind. Most avian and human IAVs have preference for
cases of natural infections with A(H1N1)pdm09 influenza viruses specific receptor types having glycans with sialic acid residues in

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Borland et al. Influenza A Virus in Dogs and Cats

α-2,3 (avian receptor) or in α-2,6 (mammalian receptor) linkages emerging and contemporary CIV-H3N8 isolates, revealed that
(63). Because canine and feline upper and lower respiratory tract significant antigenic drift may have occurred. Altogether since
epithelium display α-2,3 sialic acid receptors, direct transmission its introduction into the canine population, evolution dynamics
of avian influenza subtypes from poultry to dogs or cats is studies of CIV-H3N8 suggested that it evolved and diverged into
possible (11, 64). Transmission mechanisms have been mostly multiple lineages (81).
documented for CIV-H3N2 infection, even though up-to-date,
other natural infections with avian IAV types have been reported Human Interspecies Transmission
in China: H9N2 (65, 66), H5N1, H5N6 (67), H5N2 (68). To date, serological evidence suggest that cats and dogs could
In most canine H3N2 cases reported, genetic analysis showed be infected worldwide with human seasonal A(H1N1)pdm09
that all genes of the isolates were closely related to an avian and H3N2 strains probably by direct transmission from their
H3N2 IAV, suggesting that the entire genome of the avian owners (31, 32, 82, 83). Several points support this hypothesis:
influenza virus had been transmitted to dogs with no sign of (i) in most cases reported so far, animal caretakers or owners
gene reassortment (10, 11, 69). The virus was found to be most had themselves history of flu-like illness and for some of them
widespread in kennels and in meat dog farms, likely due to the confirmed by PCR; (ii) susceptibility of cats and dogs correlated
close physical contact between infected poultry and dogs in these well with influenza prevalence in the human population and
host-dense environments (16, 69, 70). From a molecular stand even followed a seasonality pattern as in humans, and (iii) virus
point, most H3N2 canine isolates were found to have at least isolation and sequence analysis of all eight genes of the canine
two mutations in the HA proteins (Ser159Asn and Trp222Leu) isolates showed high nucleotide similarity thus suggesting that
that may have facilitated H3N2 influenza A virus jump from human viruses could therefore jump into dogs and cats, without
birds to dogs (52, 71). Furthermore, it is likely that gradual prior adaptation. However, details about molecular determinants
accumulation of mutations throughout the eight gene segments potentially related to transmission have not been unraveled so far.
may have resulted in specific adaptation of H3N2 into canids
(69, 72), although the evolutionary rate of the NA segment was
higher than the seven others (69). This is further supported by SUBTYPES AROSE FROM GENETIC
the fact that (2012–2013) Korean canine H3N2 isolates replicated REASSORTMENT
at higher titer and induced more severe clinical symptoms than
2009 isolates, clearly indicating that the canine H3N2 virus is Major attention has traditionally focused on swine as key
continuously evolving in the canine population. mammalian “mixing vessels” hosts for the reassortment of
Noteworthy, CIV-H3N2 further acquired the ability to influenza viruses from different host species (84). As both α-2,3
naturally infect cats, as first reported in a Korean animal shelter sialic acid receptors and α-2,6 receptors residues are distributed
(15) (Table 1). Genomic sequence analysis of H3N2 feline isolate throughout its respiratory tract, swine serve as a vehicle for
displayed high sequence similarities (98.0–99.8%) with canine influenza virus genetic reassortment, allowing avian, swine,
H3N2 isolate, thus suggesting that CIV-H3N2 can be naturally and human IAVs subtypes to reassort following co-infection.
transmitted from dogs to cats without prior adaptation (15, 73, Knowing that both receptors have been found in dog and cat
74). Hence, this indicates that cats may play an intermediate respiratory organs, as revealed by lectin histochemistry analyses
host role in transmitting the H3N2 virus among feline and (37, 85, 86), dogs and cats could be dually or sequentially infected
canine species. with avian- and/or mammalian influenza viruses, making them
possible hosts for the generation of a viruses with novel genome
Equine Interspecies Transmission combinations, with epidemic and/or pandemic potentials.
Canine H3N8 originated after the transfer of an equine influenza Different genetic reassorted subtypes have arose in dogs
virus (EIV), likely through close contact with infected horses (Table 1, Figure 1). During a surveillance effort in 2012 in South
(7). Phylogenetic analysis of the HA H3N8 viral genomic Korea, a novel strain of the H3N1 subtype was isolated from
sequences from horses and dogs highlighted that all canine H3N8 canines, and whole-genome sequencing showed that it contained
sequences clustered together in a single monophyletic group, the HA gene segment from CIV-H3N2 and the remaining seven
distinct from EIV (7). So far, no evidence of reassortment with other gene segments from human A(H1N1)pdm09 (35). Since
other subtypes has been reported. A comparison of equine and then, at least four other reassortants involving CIV-H3N2 and
canine H3N8 sequences highlighted key amino acid residues that A(H1N1)pdm09 have been isolated from dogs in Southern Asia,
may be involved in receptor binding specificity and host cell including a CIV-H3N2 harboring the M gene segment of human
tropism (38, 75, 76). Interestingly, as for H3N2, structural, and A(H1N1)pdm09 (36, 87). The emergence of these novel CIV-
receptor binding analyses support the role of the HA Trp222Leu H3N2 reassortants likely arose through co-infection of CIV-
mutation in facilitating viral interspecies transmission from H3N2 and A(H1N1)pdm09 virus, correlating with high co-
equine to canine (77–79). However, CIV-H3N8 has not been positivity for both canine H3N2 and A(H1N1)pdm09 antibodies
found to be phenotypically different from equine H3N8 strains in in the canine population (11, 35). Remarkably, multiple genomic
terms of replicability and infectivity, thus suggesting that cross- reassortment between swine-origin subtypes of the H1N1 and
species transmission and adaptation of influenza viruses may endemic canine H3N2 lineages co-circulating in dogs were
be rather mediated by subtle changes in virus biology (76, 80). recently reported in pet dogs in China (Table 1) (88). Moreover,
Furthermore, recent analyses of the amino acid sequence from in a large-scale analysis of sequence data of IAVs from various

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Borland et al. Influenza A Virus in Dogs and Cats

species, the NS gene of a CIV-H3N2 subtype isolated from a of interspecific cat-to-human spill-over has been reported, and
Chinese dog in 2007 was found to be closely related to H5N1 this occurred after prolonged and unprotected exposure to ill cats
avian influenza viruses, indicating that reassortment may also and their respiratory secretions, which indicates that risk for cat-
have occurred between canine H3N2 and avian H5N1 (89). Of to-human transmission is low (91). Rather infected humans may
particular concern, some CIV-H3N2 reassortants demonstrated be the source of pet infection, and the combination of reverse
the ability to infect and efficiently transmit to cohoused dogs zoonosis (from humans to pets), potential co-infections and gene
in experimental settings, thus supporting potential adaptation of reassortment may provide a favorable ecosystem for crossing
novel subtypes to canine populations (36, 80). species barrier between pets and humans.
In cats no reassortment between avian and mammalian IAVs In light of reported epidemiological evidences and current
was thought to occur until recently, where a novel reassortant of knowledge of the molecular mechanisms behind interspecies
the H5N6-subtype influenza viruses was isolated from two cats transmission and genetic reassortment, it seems of significant
in eastern China (90). Both viruses were sequenced and genetic importance to enhance active surveillance of cats and dogs
analysis showed that these viruses received their genes from three under the framework of “One World, One Health,” warranting
avian subtypes, including H5N6 (HA, NA, PA), H9N2 (PB2, M, control and prevention of IAV infections as the threat of an
NS), and H7N9 (PB1, NP) influenza subtypes viruses isolated influenza pandemic is a concern. Notably, implementing large
in China (Figure 1). Analysis of the receptor-binding preference scale programs of IAV antibody serosurveillance in canine and
of the feline isolated H5N6 virus revealed that it possesses both feline populations may serve as sentinels for monitoring the
avian- and human receptor specificities. Furthermore, the H5N6 overall risk of human exposure to emerging zoonotic influenza
virus was able to replicate to high titer in the lungs of infected viruses. Moreover, information on influenza viruses circulating
in mice without prior adaptation, though it was not lethal, in canine and feline populations is also crucial for the selection
indicating mammalian host adaptation (90). of viruses for effective vaccination programs targeting high
risks dog populations (92) and will undoubtedly aid in the
DISCUSSION prevention and control of future epidemics. The advent of
rapid molecular diagnostic tests such as real-time PCR and
Evidences exist that companion dogs and cats can have a dual unbiased next generation sequencing that can directly detect viral
role as influenza A virus hosts, by (i) sustaining inter- and pathogens and combined with specific subtyping (i.e., H3N8 and
intraspecific transmission and (ii) generating novel IAV through H3N2 in dogs; H1N1 and H7N2 in cats) should also provide
recombination. Although most cases of natural cross-species earlier warning and enable a more appropriate outbreak control
infections have resulted in limited onward transmission in dogs in case of respiratory illness symptoms in cats and dogs. As
and cats, two influenza subtypes are now continuing to circulate the genesis of these emerging viruses is not well-understood,
in dogs (CIV-H3N8 and CIV-H3N2). While the role of cats is further research aiming at investigating the ecology, evolution
less clear and less documented, they still appear to be susceptible and mechanisms of IAV at the human–animal interface will
mainly to avian influenza infections, even though most of them help to better understand which virus pose a serious threat
seem to be rather subclinical (reservoirs). This should be a cause to humans.
of concern, especially for feral and free-roaming cats that tend to
have less controls and closer contact with birds and other farm AUTHOR CONTRIBUTIONS
animals. However, it can be also assumed that because of the
feline social organization that prevents direct cat-to-cat contact SB performed the review, collected data form literature, and
required for viral transmission, the virus may transmits very wrote the manuscript. JY-M conceived the idea of the review
inefficiently among feline population. and helped to revise the manuscript. PG, MJ, and FM revised
Moreover, several lines of evidence suggest that dogs and and provided first feedback for the manuscript. All the authors
cats should be considered as mixing vessels for the reassortment contributed to manuscript revision, read, and approved the
of novel influenza viruses. Notably, canine influenza viruses, submitted version.
and more particularly those of the CIV-H3N2 subtype, have
reassorted multiple times with avian- and mammalian- adapted ACKNOWLEDGMENTS
influenza viruses since their time of emergence, clearly showing
that the gene pool of avian, human, and canine viruses is The authors would like to thank Stéphane Dubreux (bioMérieux
indeed compatible. These new viruses could further spread S.A), Dr. Pierre Rouppert (bioMérieux S.A), and Dr. Kenneth
widely among household dogs and cats and may therefore Leroy (bioMérieux S.A) for their review, support, and comments
represent a threat for human health. Up to date only one case in regards to the relevance for veterinary practitioners.

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88. Chen Y, Trovao NS, Wang G, Zhao W, He P, Zhou H, et al. Emergence and is an employee of BioFire Diagnostics LLC.
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China. MBio. (2018) 9:e00909–18. doi: 10.1128/mBio.00909-18 Copyright © 2020 Borland, Gracieux, Jones, Mallet and Yugueros-Marcos. This is an
89. Zhu H, Hughes J, Murcia PR. Origins and evolutionary dynamics of open-access article distributed under the terms of the Creative Commons Attribution
H3N2 canine influenza virus. J Virol. (2015) 89:5406–18. doi: 10.1128/JVI. License (CC BY). The use, distribution or reproduction in other forums is permitted,
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90. Cao X, Yang F, Wu H, Xu L. Genetic characterization of novel reassortant original publication in this journal is cited, in accordance with accepted academic
H5N6-subtype influenza viruses isolated from cats in eastern China. Arch practice. No use, distribution or reproduction is permitted which does not comply
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