00.073.0.01.027.
Western equine encephalitis virus
Cite this publication
as: Calisher, C.H. (2003). 00.073.0.01.027. Western equine encephalitis virus . In:
ICTVdB - The Universal Virus Database, version 4. Büchen-Osmond, C. (Ed),
ICTVdB Management, The Earth Institute and Department of Epidemiology, Mailman School of Public Health, Columbia
University, New York, NY, USA.
Cite this site as: ICTVdB - The Universal
Virus Database, version 4.
http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/
Isolate
designation: Original reference strain (=California horse).
Isolation date: October; 1930.
Location: Merced County; California; the United States of America.
Source of isolate: horse (Equus caballus).
Virus was isolated by Dr Karl F. Meyer; Hooper Foundation;
University of California; Berkeley; California; the United States of America.
Reference: Meyer KF, Haring CM, Howitt B (1931). The etiology of
epizootic encephalomyelitis of horses in the San Joaquin Valley. Science
74:227-228.
Classification
This is a description of an
invertebrate and vertebrate virus at the species
level with data on all virus properties from morphology to genome,
replication, antigenicity and biological properties.
ICTVdB Virus Code: 00.073.0.01.027. Virus accession number:
73001027. Former Virus Code: 73.01.0.027; former accession number:
73010027.
NCBI TaxID:
[11039].
Biocontainment Level
Health authorities
recommend to handle this virus at the biocontainment level BSL-2.
Name, Synonyms and Lineage
The taxon has the
accepted ICTV name (Western equine encephalitis virus). ICTV approved
acronym: (WEEV). Virus is an ICTV approved species. Virus is assigned to the
genus 00.073.0.01. Alphavirus; family 00.073. Togaviridae; not
assigned to an order.
Introduction
Symptoms in the host are well established and the causative agent is determined.
Distinct viral structures are visible in thin sections of infected tissue.
Particles contain nucleic acid. Nucleic acid of virions is
encapsidated. Size and shape of virus has been determined by electron
microscopy.
Virions have a complex construction and consist of an envelope
and a nucleocapsid. During their life cycle, virions have a cell-associated
cycle; occur in one phenotype only. Virions are enveloped by a single
layer envelope and mature naturally by budding through the membrane of
the host cell. Virions are spherical and 70 nm in diameter. The
envelope surrounds one nucleocapsid and has surface projections.
The surface projections are distinctive spikes composed of different types of
proteins that are evenly covering the surface. They are evenly
dispersed and embedded in a lipid
bilayer. The surface projections comprise hemagglutinin, are glycosylated and antigenic
and are formed by
proteins, designated E1 and E2, which exhibit hemagglutinin
activity. Host ribosomes are not seen inside the envelope. A regular capsid
structure is present. Capsid/nucleocapsid is round and exhibits
icosahedral symmetry (T = 4). The nucleocapsid
is isometric and has a diameter of 40 nm. The capsid shells of
virions are composed of a single layer. Capsids appear round. Nucleocapsid
contains a nucleoprotein complex.
Virion populations are comprised of particles of uniform size. Capsids all
have the same appearance and only one species is recovered in
preparations.
The molecular mass (Mr) of virions is 52 x 106.
Virions have a buoyant density in sucrose of 1.22 g cm-3. The
sedimentation coefficient is 280 S20w. Virion infectivity is
inactivated; destroyed by heating for 10 min above
56°C. Extent of effect on virion infectivity is reduced (by heat). Under
in vitro conditions virions are stable when stored at -70°C;
relatively stable when stored at -40°C; not stable when stored at
-20°C (or above), or 37°C (half-life about 7 hours); inactivated
in acid environment of pH 1-3; stable in alkaline
environment of pH 7-9. Virions are sensitive to treatment with lipid
solvents, detergents, ether, trypsin, chloroform, formaldehyde, heat, and
ß-propiolactone. The infectivity is reduced after exposure to irradiation.
The
genome is monomeric, not segmented, consists of a single molecule
of linear positive-sense single-stranded
RNA. The genome is infectious. Minor species of genomic nucleic acid are
not found. The complete genome is 11484 nucleotides long. Sequence(s) can be
accessed at GenBank; the RNA has been partially sequenced
and has the accession numbers
[J03854] (strain
BFS1703); [U01065] (isolate 5614);
[AF109297] (strain Fleming);
[AF214040] (strain 71V-1658, complete genome). The
sequenced region is up to 4500 nucleotides long and
encodes C, E1, E2, nsP1, nsP2, nsP3, nsP4. Nucleotide sequences at the
3'-terminus are identical (polyadenylated), or unrelated to the
5'-terminus. The 5'-end of the genome has a cap. The 3'-terminus
has no long non-coding region; has conserved nucleotide sequences. The
3'-terminus has a poly (A) tract. Each virion contains a single copy of the
genome; a full length copy. Reference to nucleotide sequence Medline ID:
[88320369];
[94025587];
[98090398].
Proteins
have been characterized and functions are assigned to them. Particles are made
up of 3 proteins. The viral genome encodes structural and
non-structural proteins. Virions consist of 3 structural proteins
located in the envelope (E1, E2), nucleocapsid (CP).
Structural Proteins: Nucleocapsid protein CP has a
molecular mass of 30-33 kDa. It is the product of the polyprotein encoded on
the 3’ end of the genome by the S-ORF, as are the other structural
proteins.
Non-Structural Proteins: Virus-coded non-structural
proteins have been identified by sequence analysis and 4
non-structural protein(s) are found (nsP1, nsP2, nsP3, nsP4). The virus codes
for enzymes and replication-associated proteins an RNA-dependent RNA
polymerase. In addition to the polymerase, the virus codes for enzymes such as
helicase, protease, synthetase, and replicase. The non-structural proteins are
thought to be involved in capping of viral RNAs, initiation of negative strand
RNA synthesis, processing of non-structural proteins, in RNA replication, the
formation of a replicase complex for the minus strand synthesis, and the
synthesis of the plus strand. The non-structural proteins function in the
cytoplasm of infected cells. Non-structural protein nsP1 has a function
assigned. The protein is coded from NS-ORF; a replication-associated protein
(capping of viral RNAs and initiating negative strand RNA synthesis) and possesses
methyltransferase activity. Non-structural protein
nsP2 has a function
assigned. The protein is coded from NS-ORF. The
protein is a replication-associated protein (functions as a protease to process
the nonstructural proteins, and as a helicase for RNA replication).
Non-structural protein nsP3 has a function
assigned; the protein is coded from NS-ORF.
Lipids are
present in significant amounts and are located in the
envelope. Virions are composed of 30% lipids by weight. The lipids are of host
origin and composition depends on the cell in which the virus replicates and are
derived from host cell membranes. Viral membranes include
phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl serine,
cholesterol, and sphingomyelin. Lipids are essential for infectivity.
Carbohydrates are found in virions; are present as glycoproteins; are N-linked
glycans and contain mannose. Carbohydrate composition in the
virion is virus-dependent.
Genome Organization and Replication
By itself, genomic nucleic acid is infectious.
Infection and Replication: Virus
replication is initiated by the insect host; occurs in the midgut and proceeds
to salivary glands. In the vertebrate host virus replication occurs in
various organs. Replication is not restricted to a particular tissue or organ of
the host. Although severity of illness depends on route and dose, the majority
of infections are subclinical, or mild. Infection involves a noncytocidal
productive infectious cycle (in the invertebrate host), or does not involve a
noncytocidal productive infectious cycle (in the mammalian host). Infected cells
continue to grow slowly (cells from arthropods), or do not continue to grow
(cells from vertebrates).
Transcription: The 5' ends of mRNAs
are capped. The 3' ends of mRNAs possess a poly (A) tract.
The virus is serologically
related to all viruses in the genus Alphavirus. Antigenic determinants
may be found on envelopes, spikes, and nucleocapsids and correspond
to each of the major structural proteins, structural glycoproteins, and
non-structural proteins; correspond to each of the major virion proteins CP, E1,
E2, nsP1, nsP2, nsP3, nsP4. The type-specific antigenic determinants are
involved in antibody mediated neutralization and hemagglutination inhibition.
Antigenic determinants that possess serogroup-specific reactivity are found on
the nucleocapsids. The serogroup-specific antigenic determinants are involved in
antibody mediated neutralization, hemagglutination inhibition, and complement
fixation. Antigenic specificity of the virion can be determined by
neutralization tests, hemagglutination inhibition tests, complement fixation
tests, ELISA tests, and immunofluorescence assays. In gel-diffusion tests
antisera display cross-reactivities among different members of the taxon.
Serological relationships between different members are very close (but
relationships depend on antigenic complex membership). Cross-reactivity is
found between isolates of the same species and species, but
not genera. Protective immunity is induced in the form of neutralizing
antibodies. Virions are usually satisfactorily stabilized for use as antigens or
immunogens by fixation with glutaraldehyde (or any of many other fixatives). The
virus is immunogenic. The virus serves as an efficient immunogen when
animals are infected with whole, disrupted or denatured virus particle preparations. These
preparations produce antibodies. The virus induces antibodies with distinct
reactivities to the subtype-specific determinants, type-specific determinants,
serogroup-specific determinants, complex-specific determinants, and
genus-specific determinants. The virus induces the formation of neutralizing
antibodies, hemagglutination inhibiting antibodies, and complement-fixing
antibodies. Antibody response that is protective against infection is usually
directed against virion glycoproteins and virion surface proteins. The serotype
is defined by E proteins. The virus serotype is determined by a serum
neutralization test; using polyclonal antibodies. Antigenic distances between
individual species, expressed as serological indices, are correlated with the
degree of sequence difference in their coat protein (E1 and E2). Species that
are serologically interrelated have antigenic homologies with different isolates
of the same virus species. Although the degree of antigenic specificity varies
with the degree of relatedness, the antigenicity is considerable between
isolates of the same virus species and species of the same serogroup.
Some species in the genus are related antigenically. They are sharing
some epitopes in the structural proteins (40% homology between species), or in
the non-structural proteins (60% homology between species). The virus is closely
related to other viruses of the WEEV complex and related to all
other alphaviruses. Classification of members of this taxon is based on their
sequence homologies. Minor biological differences have been recognized between
WEE virus isolates. Most closely homologous to other viruses of the WEEV
complex.
Diagnostics and Reference Collections
The
best tests for diagnosis are PCR, neutralization, IgM and IgG ELISA, Hi, CF,
IFA. Antisera are commercially available from American Type Culture Collection
and W.H.O. regional reference centers.
Vaccines
Commercial or experimental vaccines are not
licensed for use in humans. Vaccines are restricted for use in humans.
Natural Host
Range
Viral hosts belong to the Domain Eucarya.
Domain Eucarya
Kingdom Animalia.
Kingdom Animalia
Phylum Arthropoda and
Chordata.
Phylum Arthropoda
Subphylum Hexapoda; Class
Insecta.
Phylum Chordata
Subphylum Vertebrata; Class
Mammalia.
Class Mammalia
Order Primates;
Family
Hominidae; virus infects Homo sapiens (human).
Host details on isolation Virus was isolated
from an adult insect.
Natural hosts and symptoms
General Symptoms in Animals
Infection can
affect the nervous system, brain, and dermis, mucosa or epithelium. General
symptoms include headache, or malaise, or photophobia, or prostration, or
pyrexia, or retardation, or stiff neck, or tremor, or uncoordination. Lesions
are found in nerve tissue. Signs and symptoms include meningitis, paralysis,
sequelae, seizures, encephalitis.
Severity and Occurrence of Disease
Host
1: Signs and symptoms may vary, but are usually mild and
disappear soon after infection. Prevalence of viral infection is seasonally
dependent, and incidences of virus infection are usually observed in summer, or
autumn, or during a wet season followed by a dry season.
Contagiousness is not observed.
Virus infects during its life cycle arthropod and vertebrate hosts.
Virus has an enzootic cycle and is transmitted from its arthropod vector to
birds and its arthropod vector to an incidental incompetent host (dead end
host).
The virus is transmitted by a vector in a direct manner.
The virus is transmitted by mechanical inoculation (usually only under
laboratory conditions); through an injection; not transmitted by contact between
hosts. Viral transmission by vectors is frequent.
Vector Transmission: The virus is transmitted by arthropods;
insects of the order Diptera; family Culicidae,
Culicinae (culicine mosquitoes). The virus is transmitted in a persistent
manner; retained when the vector moults; circulates in hemolymph; replicates in
the vector; does not require a helper virus for vector transmission.
Non-Vector Transmission: The likelihood of viral transmission
by respiratory, by faecal-oral route, by direct contact,
through sexual contact, by parenteral transmission, through
blood or blood products, congenital (germ line) transmission,
transplacental transmission, perinatal transmission
is nil.
Experimental Hosts and Symptoms
Under
experimental conditions susceptibility to infection by virus is found in many
families.
Host 1: Experimentally infected hosts mainly show symptoms of
encephalitis with ensuing death.
Cell lines or tissue cultures susceptible to infection are derived from chicken
or duck embryos, hamster kidney, monkey kidney, HeLa cells and other human cells.
Symptoms include cytopathic effects, plaques.
Diagnostic Hosts
For virus isolation
the most commonly used test animals are suckling mice; cell lines or tissue
cultures are chicken embryo, duck embryo, Vero cells. Virus has been propagated
in experimental animals, cell culture, and developing embryo.
Maintenance and Propagation Hosts
Most commonly used maintenance and propagation host species are suckling mice,
Vero cells. Virus is propagated in embryonated eggs of chicken and duck. Virus
is propagated in embryonated eggs by inoculating the amnion.
Assay Hosts
Host 1: Most
commonly used species for assaying the virus are suckling mice, Vero cells.
Pathology
The virus can be detected best in
the nervous system; brain tissue, or liver.
Histopathology: Histopathologic lesions are found in brain.
Virions are found in the cytoplasm. Primary histological changes include
inflammation and necrosis.
Location of first isolation is -120 degree longitude
(west); 37 degree latitude (north). The virus is known to occur in temperate
regions, subtropical regions, and tropical regions; viral host lives in the
atmosphere. The viral host is found in a pristine environment with no signs of
human interference and a undisturbed environment yet with signs of human
disturbance an agricultural environment, or an aquatic environment; a populated
environment. The virus occurs in Argentina, Belize, Brazil, Canada, Cuba,
Ecuador, Mexico, the United States of America, and Uruguay.
Studies
reported by Reeves WC (1990) Calif. Mosq. and Vector Control Assoc.,
Inc., Sacramento, CA; 508 pages. A fact sheet on this virus is available from
the Centers for Disease Control and Prevention (CDC),
National Center for
Infectious Diseases (NCID)
Fact sheet.
Epidemiological
surveillance activities are overseen by Centers for Disease Control and
Prevention (CDC) various state and national laboratories throughout the western
hemisphere).
Data have been submitted online to ICTVdB on 20-03-2002 by
Charles H. Calisher
AIDL, Department of Microbiology, Immunology, and
Pathology
Colorado State University
Foothills Campus
Fort Collins;
Colorado; 80523
U.S.A.
Tel: + 001-970-491-2987.
Fax:
+ 001-970-491-8323.
Email: calisher@cybercell.net.
