Introduction

Alphaviruses are members of the Togaviridae family of icosahedral, enveloped, single-strand, message-sense RNA viruses. The mosquito-borne alpha-viruses are important causes of encephalomyelitis in the Americas and are on the category B list of agents of biodefense concern. Eastern equine encephalitis (EEE), western equine encephalitis (WEE), and Venezuelan equine encephalitis (VEE) viruses are the neurotropic alphaviruses of greatest importance as causes of human encephalomyelitis and were initially recognized for their ability to cause disease in horses. Semliki Forest virus (SFV) and Sindbis virus (SINV) do not usually cause encephalitis in humans, but are studied frequently in mice as model systems for alphavirus encephalomyelitis.

EEE virus (EEEV) was first isolated in 1933 from the brains of horses during an epizootic of equine encephalitis in Virginia and New Jersey [1] and was demonstrated to cause human encephalitis in 1938 [2]. In the summer of 1930 a similar equine epizootic occurred in the San Joaquin Valley of California and WEEV was isolated from the brains of affected horses [3], followed in 1938 by recovery of the same virus from the brain of a child with fatal encephalitis [4]. A related WEEV complex virus, Highlands J virus (HJV), was isolated in the eastern part of the United States in 1952 [5, 6]. In 1936, an outbreak of equine encephalitis spread from Colombia into Venezuela, the virus isolated from the brains of affected horses was antigenically distinct from EEEV and WEEV and became the third encephalitic alphavirus identified in the Americas [7, 8].