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VEE Virus

I. General Information

1. NCBI Taxonomy ID:

2. Disease:

Venezuelan equine encephalitis

3. Introduction

Venezuelan equine encephalitis virus (VEEV) is a naturally emerging disease threat and a highly developed biological weapon. VEEV is the most important human and equine pathogen of the New World alphaviruses (Togaviridae: Alphavirus). VEEV causes periodic outbreaks of febrile and neurological disease. VEE was first recognized as a disease of horses, mules, and donkeys in northern South America during the 1930s. VEEV, was first isolated in 1938 from the brains of fatal equine cases in Yaracuy State, Venezuela. VEEV is a spherical virus 70 nm in diameter and a messenger-sense, single-stranded RNA genome approximately 11,400 nucleotides in length (Weaver et al., 2004).

4. Microbial Pathogenesis

In equines and humans, VEEV causes inapparent to acute encephalitis. Enzootic VEE strains in subtypes I-E, II, III, and IV are avirulent for equines and generally produce only low titered viremia and little or no illness. However, at least some of the enzootic viruses can be pathogenic for humans and have caused fatal disease. The incubation period in human VEEV infection is usually 2–5 days. VEE occurs in all human age groups without sex bias. Children are more likely to develop fatal encephalitis than adults. VEEV also causes birth defects, abortions and stillbirths in pregnant women. In experimentally infected equines and rodents, VEEV causes severe myeloid depletion in bone marrow and lymphocyte destruction in lymph, nodes and spleen. Encephalitis is accompanied by a wide range of histopathology, from mild neutrophilic infiltration to neuronal degeneration, necrotizing vasculitis, and Purkinje cell destruction. In mice, VEEV appears to reach the brain via the olfactory nerve, seeded by viremia (Weaver et al., 2004).

VEEV encodes four nonstructural proteins (nsP1–4) and three structural proteins: the capsid and the E1 and E2 envelope glycoproteins. The E2 protein forms spikes on the surface of the virion. The E1 protein lies adjacent to the host cell–derived lipid envelope. VEEV can use the laminin binding protein as a receptor for entry into cells via receptor-mediated endocytosis. After fusion of virions with the membrane of endosomes at low pH via a hydrophobic amino acid sequence in the E1 protein, the genome is translated in the cytoplasm to generate the nonstructural polyprotein. Viral genome replication occurs on the cytoplasmic surface of endosomes. One molecule of genomic RNA interacts in the cytoplasm with 240 copies of the capsid protein to form a nucleocapsid. The envelope glycoproteins are inserted into the endoplasmic reticulum membrane and interact with nucleocapsids at the plasma membrane to initiate budding of virus particles on the surface of cells (Weaver et al., 2004).

Biological transmission of arthropod-borne VEEV involves initial infection of the mosquito midgut following ingestion of a viremic blood meal. Posterior midgut epithelial cells become infected first, followed by dissemination into the hemocoel and infection of secondary organs and tissues including the salivary glands. Virus maturation (budding) in midgut epithelial cells occurs exclusively on the basal margins adjacent to the basal lamina (Weaver et al., 2004).

The epizootic transmission cycle of VEEV actively involves equines as highly efficient amplification hosts. Although the vertebrate host range of epizootic VEEV strains is wide and includes humans, sheep, dogs, bats, rodents, and some birds, major epidemics in the absence of equine cases have never occurred despite the repeated occurrence of epizootics near major cities such as Maracaibo (Weaver et al., 2004).

Sylvatic rodents in the genera Sigmodon, Oryzomys, Zygodontomys, Heteromys, Peromyscus, and Proechimys are believed to be the principal reservoir hosts of most enzootic VEE complex viruses. They are frequently infected in nature. They also have high rates of immunity and develop moderate to high titered viremia (Weaver et al., 2004).

5. Host Ranges and Animal Models

VEE causes encephalitis in a wide range of vertebrate animals including humans, horses, mules, donkeys, sheep, dogs, bats, rodents, and some birds. Rodents have been frequently used in the laboratory for VEEV pathogenesis and vaccine studies. VEEV is also an arthropod-borne virus and can infect and replicate in mosquito (Weaver et al., 2004).

6. Host Protective Immunity

Cell-mediated immunity plays a predominant role in protection against VEEV. Immunity resulting from inactivated VEEV vaccines is short-lived and frequent boosters are required to maintain protection. Inactivated VEEV vaccines generate protective neutralizing immunity only after multiple inoculations (Weaver et al., 2004).

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