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Descriptions are generated automatically from the ICTVdB database including links. Some descriptions are only very basic and links may point to documents that are not yet published on the Web.

00.073.0.01.008. Eastern equine encephalitis virus

Cite this publication as: ICTVdB Management (2006). 00.073.0.01.008. Eastern equine encephalitis virus. In: ICTVdB - The Universal Virus Database, version 4. Büchen-Osmond, C. (Ed), Columbia University, New York, USA

Cite this site as: ICTVdB - The Universal Virus Database, version 4. http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/

Isolate Description

Isolation date: 03 March 1933.
Location: North America; the United States of America.

Host of Isolate and Habitat Details
Source of isolate: horses.
Virus was isolated from adults.

Collection and Isolation Details
Virus was isolated by Ten, Broeck and Merrill. The United States of America.

Reference to Isolation Report
Ten, Broeck & Merrill (1933). Proc. Soc. Exp. Biol. Med. 31 217-220.

Biocontainment Level

Distribution of this virus falls under quarantine restrictions. It is recommended to handle this virus at the biocontainment level BSL-3.

Classification

This is a description of an invertebrate or vertebrate virus at the species level with data on all virus properties from morphology to genome, replication, antigenicity and biological properties.

ICTVdB Virus Code: 00.073.0.01.008. Virus accession number: 73001008. Obsolete virus code: 73.0.1.0.008; superceded accession number: 73010008.
NCBI Taxon Identifier NCBI Taxonomy ID: 11021.

Name, Synonyms and Lineage

The taxon has the accepted ICTV name.

ICTV approved acronym: (EEEV). Virus is an ICTV approved species. Virus is of the genus 00.073.0.01. Alphavirus; of the family 00.073. Togaviridae; not assigned to an order.

Virion Properties

Symptoms in the host are well established and the causative agent is determined.

Distinct viral structures are visible in thin sections of infected tissue and nucleic acid of virions is encapsidated. Size and shape of virus has been determined by electron microscopy.

Virion Properties

Morphology

Virions consist of an envelope, spikes, and a nucleocapsid. During their life cycle, virions have not been observed outside a cellular environment and have a cell-associated cycle and occur in one phenotype only. Virus capsid is surrounded by a single layer envelope and virions mature naturally by budding through the membrane of the host cell. Virions are spherical and measure 60-65 nm in diameter. The envelope surrounds one nucleocapsid. Envelope has surface projections. Surface projections are distinctive, knob-shaped spikes that are evenly dispersed covering the entire surface and are embedded in a lipid bilayer which is comprises hemagglutinin. Surface projections are composed of different types of glycosylated proteins which determin the anigenecity. The projections 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.

Physicochemical and Physical Properties

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 S_20w. Virion infectivity is inactivated and 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 at -20°C or above, or 37°C (half-life about 7 hours). Virions are inactivated in acid environment of pH 1-3, but are 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.

Nucleic Acid

The genome is monomeric; not segmented and contains 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 11675 nucleotides long. Sequence can be accessed from GenBank. The RNA is fully and partially sequenced. Complete sequence is 11675 nucleotides long and sequenced region is 508 nucleotides long, or 1100 nucleotides long and encodes 6K, C, E1, E2, E3, nsP1, nsP2, nsP3 and nsP4. Sequence has the accession number
[AF525498]; [AF525497]; [X63135], and the NCBI reference genome has the accession number [NC_003899]. Nucleotide sequences at the 3'-terminus are identical and unrelated to the 5'-terminus. The 3'-terminus has no long non-coding region; conserved nucleotide sequences; of 19 nucleotides in length; in species of same genus. 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 in PubMed: reference(s). GenBank records for nucleotide sequences; complete genome sequences.

Proteins

Proteins have been characterized and functions are assigned to them. Particles are made up of 3 proteins.

The viral genome encodes structural proteins and non-structural proteins. Virions consist of 5 structural protein(s) located in the envelope (E1, E2, E3), nucleocapsid (C) (6k). The viral envelope contains 3 integral membrane proteins.

Structural Proteins: Envelope protein E1. Envelope protein has been sequenced and a function assigned (E1 is 439 amino acids long and is postulated to serve as a fusion protein which possess(es) entry function into the cell. Envelope protein E2 has been sequenced and a function assigned (E2 is 423 amino acids long, is a transmembrane protein. During post-translational processing envelope protein modifications occur that include glycosylation. Envelope protein E3; has been sequenced and a function assigned (E3 is 60 amino acids long, is an attachment protein which possess(es) probably a signal function for E2. Nucleocapsid protein C; has a molecular mass of 30000 Da; is the product of the polyprotein encoded on the 3' end of the genome by the S-ORF, as are the other structural proteins; has been sequenced.

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, or replication-associated proteins; an RNA-dependent RNA polymerase. In addition to the polymerase, the virus codes for enzymes such as helicase, protease, replicase, and synthetase. 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; function in the cytoplasm of infected cells; polymerase nsP4. Virus coded polymerase has a molecular mass of 19 kDa. Polymerase has been sequenced. The sequence has the accession number [P89949]. Non-structural protein polyprotein 1; has a molecular mass of 277 kDa has been sequenced and a function assigned. The protein is coded from NS-ORF; a replication-associated protein (capping of viral RNAs and initiating negative strand RNA synthesis) possesses methyltransferase activity. Non-structural protein nsP2 has been sequenced and 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. Non-structural protein has been sequenced and a function assigned; the protein is coded from NS-ORF. Non-structural protein nsP4; has been sequenced, or a function assigned.

Lipids

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. Lipids are derived from host cell membranes, but have a monolayer structure in the viral membrane . Viral membranes include phosphatidyl ethanolamine, phosphatidyl choline, phosphatidyl serine, cholesterol, and sphingomyelin. Lipids are essential for infectivity.

Carbohydrates

Carbohydrates are glycoproteins and N-linked glycans that contain mannose. Carbohydrate composition in the virion is virus-dependent.

On the fly genome map for NC_003899.

Genome Organization and Replication

Virions attach to receptors located on the surface of cell membrane to enter host cells by fusion with and endocytosis of the viral envelope.

The process of intracellular uncoating of virions is understood. Virus uncoating occurs in the cytoplasm; the viral nucleocapsid is delivered to the cell cytoplasm, the site of mRNA and subgenomic mRNA transcription.

By itself, genomic nucleic acid is infectious.

Infection and Replication: Virus replication is initiated by the insect host; occurs in the midgut or 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 from arthropods continue to grow slowly and do not continue to grow (in case of vertebrates).

Transcription: The 5' ends of mRNAs are capped. The 3' ends of mRNAs possess a poly (A) tract.

Translation: The genome replicates in the cytoplasm.

Antigenicity

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 C, E1, E2, E3, 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, or hemagglutination inhibition tests, or complement fixation tests, or ELISA tests, or 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 depends on antigenic complex membership). Cross-reactivity is found. Cross-reactivity 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 virus particle preparations, or disrupted virus particle preparations, or denatured virus particle preparations. These preparations produce antibodies. The virus induces antibodies with distinct reactivities to the subtype-specific determinants, or type-specific determinants, or serogroup-specific determinants, or complex-specific determinants, or genus-specific determinants. The virus induces the formation of neutralizing antibodies, or hemagglutination inhibiting antibodies, or complement-fixing antibodies. Antibody response that is protective against infection is usually directed against virion glycoproteins, or 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, or species of the same serogroup. Some species in the genus are related antigenically. They are sharing some epitopes in the structural proteins (40% homology), or in the non-structural proteins (60% homology). The virus is closely related to other viruses of the EEV 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 EEE virus isolates. Known sequence homologies with other viruses. Sequence homologies phylogenetic analyses using nonstructural protein amino acid sequences indicate that alphaviruses evolved from a common ancestor which existed a few thousand years ago. Reliable virus detection and identification can be achieved by electron microscopy, or serological tests, or PCR techniques, or using specific primers.

Diagnostics and Reference Collections

The best tests for diagnosis are PCR, neutralization, IgM, IgG, Elisa, Hi, CF, IFA. Antisera are commercially available from American Type Culture Collection, or W.H.O. regional reference centers.

Vaccines are restricted for use in humans.

Vaccines

Vaccines are commercially available but not licensed for use in humans. Vaccines are not licensed for experimental use in humans.

Biological Properties

Natural Host

Virus infects during its life cycle arthropod and vertebrate hosts. Virus has an enzootic cycle and is transmitted from arthropod vector to birds, or arthropod vector to an incidental incompetent host (dead end host). Domain
Viral hosts belong to the Domain Eucarya.

Domain Eucarya
Kingdom Animalia.

Kingdom Animalia
Phylum Arthropoda and Chordata.

Phylum Arthropoda
Subphylum Hexapoda; Class Insecta; Subclass Pterygota (winged insects), Order Diptera.

Phylum Vertebrata
Subphylum Vertebrata.

Class Aves and Mammalia.

Class Aves Order Galliformes; virus infects Family Phasianidae.
Virus infects Gallus and Phasianus.

Class Mammalia Order Perissodactyla and Primates;
Family Hominidae.
Virus infects Homo sapiens (human,
Family Equidae: virus infects Equus caballus (horse).

General Symptoms in Animals Infection can affect the nervous system, musculo-skeletal system, 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: Infection is mosquito (Culex spp., Aedes spp.) not apparent. Prevalence of viral infection is seasonally dependent, and incidences of virus infection are usually observed in summer; after heavy rainfalls (which are followed by an increased mosquito population). The incubation period lasts usually lifetime. The mosquitoes remain persistently infected and contagious.

Host 2: Birds (chicken, pheasant). The infection is clinically expressed. Infection is apparent (Birds vary in their susceptibility, with some birds developing disease). Signs and symptoms may vary, but are usually severe; persist (EEE virus persists in the feather follicles of infected pheasants). Prevalence of viral infection is seasonally dependent, and incidences are usually observed in summer. In naturally infected hosts morbidity rate may be as high as 50-70 % (case fatality rate in birds).

Host 3: Horses (Equus caballus). Infection is apparent. The infection is clinically expressed. Although disease expression is dependent on dose, infection is usually acute. Signs and symptoms may vary, but are usually severe. The North American strains of EEE are amongst the most virulent of the alphavirus). Prevalence of viral infection is seasonally dependent, and incidences are usually observed after heavy rainfalls (which are followed by an increased mosquito population). Contagiousness is variable; the incubation period lasts usually 5 day(s). In naturally infected hosts mortality rate may approach 90 % (case fatality rate in horses).

Host 4: Under natural conditions virus infects Humans (Homo sapiens). Infection is apparent. Human infections are unusual. A median of five cases are observed in the U.S.A. among approximately 23 inapparent infections. Children are more susceptible). The infection is clinically expressed. Although disease expression is dependent on dose, infection is usually acute. Signs and symptoms may vary, but are usually severe. Prevalence of viral infection is seasonally dependent, and incidences are usually observed in summer and after heavy rainfalls (which are followed by an increased mosquito population). In naturally infected hosts morbidity rate may be as high as 5 % and mortality rate may approach 30-60 % (; children are most severely affected).

Transmission and Vector Relationships

Virus is transmitted by a vector in a direct manner. Virus is transmitted by mechanical inoculation; through an injection; transmitted by grafting; not transmitted by contact between hosts. Vector Transmission: Viral transmission by vectors is frequent.

Virus is transmitted by arthropods, by insects of the order Diptera, family Culicidae, Culicinae (culicine mosquitoes). Virus is transmitted in a persistent manner; retained when the vector moults; circulates in hemolymph; does not require a helper virus for vector transmission.

Non-Vector Transmission: The likelihood of viral transmission by respiratory route (air-borne) is low; faecal-oral route (water and food-borne) is low; direct contact is low; through sexual contact is low; through parenteral transmission is low; through blood or blood products is low; through congenital (germ line) transmission is rare; through transplacental transmission is rare; through perinatal transmission is rare.

Experimental Hosts and Symptoms

Under experimental conditions susceptibility to infection by virus is found in many families.

Host:
Experimental host is susceptible to infection mice. Experimentally infected hosts mainly show symptoms of similar neuro-virulence.

Host 2: Virus infects under experimental conditions guinea pigs, hamster, chickens, ducks.

Diagnostic Hosts

For virus isolation the most commonly used 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 chicken, duck. Virus is propagated in embryonated eggs by inoculating the amnion.

Pathology

Virus can be best detected in nervous system; musculo-skeletal tissue, or brain tissue, or liver.

Histopathology: Histopathologic lesions are found in brain. Virions are found in the cytoplasm. Primary histological changes include inflammation, or necrosis.

Geographical Distribution

Geographical distribution of the virus is probably restricted. The virus spreads in North America and South and Central Americas. The virus is known to occur in temperate regions, or subtropical regions, or tropical regions; viral host lives in the atmosphere. The viral host is found in a pristine environment with no signs of human interference, or a undisturbed environment yet with signs of human disturbance; an agricultural environment, or an aquatic environment; a populated environment. The virus occurs in the United States of America and Venezuela.

Ecology, Epidemiology and Control

Epidemiological surveillance activities are overseen by Centers for Disease Control and Prevention (CDC). A fact sheet on this virus is available from the Centers for Disease Control and Prevention (CDC), National Center for Infectious Diseases (NCID) (: Arbovirus encephalitis) (Emedicine: VEEV, and Medical NBC online Information server: VEEV).

List of Strains and Isolates in the Species

82V-2137 (North American variant), CAOO-Charlie (North American variant), MA 38,

BR85-436087, PA86-435731, BR56-BeAn5122, MX97-1076, GA91-POREE, FL96-14834,

TX95-PV5-2547, FL93-939, TX91-VR1-7164, MS83-4789, LA50-arth167, CO92-49,

VE96-250714, BR83-416361, BR83-414556, BR78-348998, BR77-77U1, BR75-300851,

PE75-75U40, GU68-68U230, BR67-126650, BR65-81828, BR60-18205, 91031, 435731,

PE6 vaccine, Pan 66058-60, IVIC Pan 57151, El Delirio, 70U1104, TenBroeck, Tr24443,

GML903866, 75V-1496, GML900188, 76V-25343, GML 207963 , MARU 435731, Tr 25714,

ArgM, ArgB, ArgLL, 32-14-989, Ar5-9690, 89-42687, 91-32277, A61-1K, DV2 60-82, 74-33620,

69-7836, MP-9, 2061-88, 89-45989, NJ-1959, 89-47595, Hammon, R-35108, R53442, W-27933, JW, 7761, 08-3-0855, 664, B64-5282.01, BeAn-5122, 10365, Sanchez, WiAn 5000-03, Williams, 215-85, ME77132, NJ/60, 3076-90, Decuir, antigenic subtype of the North American variant (isolate 4789), South American strain, VA33.

Comments

This description has been compiled from data presented in the literature (Encyclopedia of Virology, Second Edition; several special articles from the journal Virology).

References

Volchkov VE, Volchkova VA and Netesov SV (1991). Complete nucleotide sequence of the Eastern equine encephalomyelitis virus genome. Mol. Gen. Mikrobiol. Virusol. 5, 8-15

Franklin RP, Kinde H, Jay MT, Kramer LD, Green EN, Chiles RE, Ostlund E, Husted S, Smith J, Parker MD (2002). Eastern Equine Encephalomyelitis Virus Infection in a horse from California. Emerging Infectious Disease 8, 283-285.

The following generic references are cited in the most recent ICTV REport .

PubMed References. A description of this taxon can also be found on the web at U.S. Centers for Disease Control and Prevention (CDC), National Center for Infectious Diseases (NCID) (and the NJ Department of Health and Senior Services).

Contributor

Data have been submitted online to ICTVdB on 26-08-2002 by Natalie Witte
Biosphere 2 Center
Columbia University
P.O. Box 689;
Oracle; A.Z. 85623, U.S.A.
email: ICTVdB Management.

The description has been generated automatically from DELTA files.

ICTVdB - The Universal Virus Database, developed for the International Committee on Taxonomy of Viruses (ICTV) by Dr Cornelia Büchen-Osmond, is written in DELTA. The virus descriptions in ICTVdB are coded by ICTV members and experts, or by the ICTVdB Management using data provided by the experts, the literature or the latest ICTV Report. The character list is the underlying code. All virus descriptions are based on the character list and natural language translations from the encoded descriptions are automatically generated and formatted for display on the Web.

Developer of the DELTA software: M. J. Dallwitz, T. Paine and E. Zurcher

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