ARENAVIRUS
ES
DR. MD. KHALID ANJUM
20.07.2018
INTRODUCTION
All arenaviruses can be divided based on their
phylogenetic and antigenic relationships into the Old
World and New World virus complexes.
The Old World complex includes arenaviruses that
circulate worldwide and in Africa, are Lymphocytic
choriomeningitis virus (LCMV) and Lassa viruses.
The New World complex includes viruses that circulate
in South and North Americas, are Junin, Machupo,
Guanarito, and Sabia viruses, and is further subdivided
into three distinct clades designated A, B, and C.
The prototypic arenavirus LCMV has a worldwide
distribution
VIRAL CHARACTERIZATION
Pleomorphic, Diameter from 50 – 300 nm, with
average diameter of 110- 130 nm.
Electron micrographs reveal a granular appearance
of the virion interior that is characteristic for all
arenaviruses and is attributed to the presence of the
host cell ribosomes.
The genome of arenaviruses consists of two single-
stranded RNA segments: large (L, 7.0kb) and small
(S, 3.4 kb).
Each segment utilizes an ambisense gene
organization to drive expression of two genes in
opposite directions.
Continued….
Lassa virus. Electron micrograph of Lassa virus in the first
Vero cell passage envelope; electron-dense interior
granules can be seen
Continued….
Genome organization and replication strategy of an
arenavirus.
Continued…
The L RNA segment encodes the viral RNA-
dependent RNA polymerase (L) and a small RING
finger protein (Z) that is the arenavirus counterpart
of the matrix proteins (M) of negative-sense RNA
viruses.
The S RNA segment encodes the glycoprotein
precursor protein and the nucleoprotein.
The glycoprotein precursor protein is post
translationally cleaved to yield two envelope
glycoproteins, GP1 and GP2, and the stable signal
peptide, which stays associated with the
glycoprotein complex on mature virions.
Continued….
Old World and clade C New World arenaviruses
utilize α- dystroglycan, a cellular receptor for
proteins of the extracellular matrix, to direct entry
into cells.
Transferrin receptor 1 (TfR1) is the primary
receptor utilized by the glycoprotein complexes of
pathogenic New World arenaviruses, however, cell
entry of nonpathogenic viruses is TfR1
independent.
Glycoproteins of pathogenic members of the New
World group can also utilize TfR1-independent entry
pathways, but less efficiently.
ARENAVIRUSES INFECTIONS
VIRUS DISEASE VECTOR DISTRIBUTION
OLD WORLD COMPLEX
Lassa Virus Lassa Fever Mouse (Mastomys West Africa
natalensis)
LCM Virus Lymphocytic House mouse worldwide
choriomeningitis (Mus musculus)
NEW WORLD COMPLEX
Junin Virus AHF Dryland vesper mouse Argentina
(Calomys musculinus)
Machupo BHF Large vesper mouse Bolivia
Virus (Calomys callosus)
Guanarito VHF Short-tailed Cane Venezuela
Virus mouse (Zygodontomys
brevicauda)
Sabia Virus BHF Unknown Brazil
REPLICATION CYCLE
The arenavirus life cycle.
PATHOGENESIS
A. RODENTS :-
Arenaviruses can cause chronic infections of their
reservoir rodents that are clinically benign.
Important variables, such as the age of animals, route
of infection, and the strain of virus determine the
outcome of infection and pathologic manifestations.
Trapping of circulating virus/antibody complexes in
the glomerulus ultimately leads to the development
of chronic glomerulonephritis.
Intracerebral injection of adult mice produces acute
fatal choriomeningitis that is characterized by
extensive infiltration by cytotoxic T cells.
Continued…
B. HUMAN :-
Limited data is available.
Very little and even absence of inflammatory
responses have been noted, and variable levels of
necrosis have been observed in liver, spleen, and
adrenal glands of LASV-infected patients.
Data from experimentally infected animals suggest
that direct viral infection of endothelial cells with
the resultant release of inflammatory mediators,
possibly from infected macrophages, is the central
mechanism that causes vascular dysfunction and,
ultimately, shock in arenaviral hemorrhagic fever.
Continued….
Patients who succumb to AHF and BHF also show
very limited histopathologic changes in tissues. No
vasculitis and virtually no inflammatory response
are observed in the organs.
Small focal hemorrhages are commonly detected
primarily in mucosal surfaces.
Hepatic necrosis is more pronounced in cases of LF
than AHF and BHF, but Councilman-like bodies are
distinctly detected in all three diseases.
Bronchopneumonia of either primary viral or, more
commonly, secondary bacterial origin is often
present.
Continued….
Concentrations of circulating endogenous interferon-α
are highly predictive of the disease outcome in
patients with AHF.
The highest levels are reached from 6 to 12 days after
the onset of specific symptoms and indicate a poor
prognosis for survival.
Experimental and clinical data suggest that
interferons and high levels of proinflammatory
cytokines may have a detrimental rather than a
beneficial effect in arenaviral infections.
Mesothelial surfaces are markedly infected with LASV.
CLINICAL MANIFESTATIONS
LYMPHOCYTIC CHORIOMENINGITIS VIRUS :-
Discovered in 1933, and widespread in Europe &
Americas.
Natural vector is the wild house mouse Mus musculus.
LCM virus is occasionally transmitted to humans,
presumably via mouse droppings, No evidence of
horizontal person-to-person spread.
LCM in humans is an acute disease manifested by aseptic
meningitis or a mild systemic influenza-like illness.
The I/P is usually 1–2 weeks, and the illness lasts 1–3
Continued…
LCM virus infections can be serious in people with
impaired immune systems.
The LCM virus also can be transmitted vertically
from mother to fetus, and infection of the fetus
early in pregnancy can lead to serious defects,
such as hydrocephalus, blindness, and fetal death.
Human cases of lymphocytic choriomeningitis
most commonly occur in autumn & Most human
infections occur among young adults.
Continued….
LASSA FEVER :-
The first isolated in 1969 from a missionary nurse,
who worked in a clinic in a small town, LASSA, in
northeastern Nigeria.
Mortality rate 15% in hospitalized pts.
In western Africa, estimates are that the annual toll
may reach several hundred thousand infections
and 5000 deaths.
I.P. :- 1- 3 wks.
Onset is gradual, with fever, vomiting, and back
and chest pain
Continued….
The disease is characterized by:-
Very high fever,
Mouth ulcers,
Severe muscle aches,
Skin rash with hemorrhages, pneumonia, and
Heart and kidney damage.
Deafness is a common complication, affecting
about 25% of patients during recovery; Hearing
loss is often permanent.
During pregnancy fetal death ˃ 75%,
In 3rd trimester MMR 30% & fetal mortality ˃ 90%.
SOUTH AMERICAN HEMORRHAGIC FEVERS
JUNIN HEMORRHAGIC FEVER (Argentine
hemorrhagic fever) :-
Major public health problem in certain agricultural
areas of Argentina.
More than 18,000 cases were reported between
1958 and 1980, with a mortality rate of 10–15% in
untreated patients.
The disease has a marked seasonal variation, and
the infection occurs almost exclusively among
workers in maize and wheat fields who are
exposed to the reservoir rodent.
Continued….
Junin virus produces both humoral and cell-
mediated immunodepression.
Deaths caused by Junin hemorrhagic fever may be
related to an inability to initiate a cell-mediated
immune response.
Administration of convalescent human plasma to
patients during the first week of illness reduced the
mortality rate from 15–30% to 1%.
An effective live attenuated Junin virus vaccine
(Candid-1) is used to vaccinate high-risk
individuals in South America.
Continued….
MACHUPO HEMORRHAGIC FEVER (Bolivian
hemorrhagic fever) :-
Identified in Bolivia in 1962.
It is estimated that from 2000 to 3000 persons
were affected by the disease, with a case-fatality
rate of 20%.
Continued….
GUANARITO VIRUS (VENEZUELAN HEMORRHAGIC
FEVER) :-
Identified in 1990.
Mortality rate of about 33%.
Its emergence was tied to clearance of forest land
for small farm use.
Continued….
Sabia virus :-
Isolated in 1990 from a fatal case of hemorrhagic
fever in Brazil.
Both Guanarito virus and Sabia virus induce a
clinical disease resembling that of Argentine
hemorrhagic fever and probably have similar
mortality rates.
DIAGNOSIS
LASSA VIRUS ;-
IgM & IgG detection by ELISA.
Immuno-histochemistry.
RT-PCR.
LCM VIRUS :-
IgM & IgG by ELISA.
Immuno-histochemical staining of tissues for viral
antigens.
RT-PCR
Viral culture using Vero cells.
PREVENTION AND TREATMENT
Prevention of arenaviral infection may be
approached by interdicting transmission;
from rodents to humans,
from person to person,
from infected specimens to laboratory workers or
by passive or active immunization.
Ribavirin is drug of choice.
Supportive care in hemmorhagic pts, by fluid
balance, electrolyte balance etc.
