Immunity Versus Immunopathology in West Nile Virus Induced Encephalitis

Abstract

West Nile virus (WNV), a mosquito-borne neurotropic pathogen, belongs to the family of Flaviviridae, the genus Flavivirus, a group of plus-sense, single-stranded RNA viruses (Anderson et al., 1999; Lanciotti et al., 1999). WNV genome is a single-stranded, positivesense RNA molecule, approximately 11,000 nucleotides in length that is translated into a single polypeptide, which is coand post-translationally processed into ten proteins – three structural proteins (envelope (E), membrane and nucleocapsid) and seven nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) (Anderson et al., 1999; Lanciotti et al., 1999). The virus was originally isolated in Africa, and later caused epidemics with mainly a febrile illness in humans in Europe, the Middle East, and parts of Asia. In 1999, a more virulent WNV strain was detected in New York City. Since then, it has rapidly spread throughout the continental United States, southern Canada, Mexico, Guatemala, the Caribbean and to several countries in South America. It has become a public health concern in North America over the past decade (Campbell et al., 2002). The virus is maintained in an enzootic cycle that involves mosquitoes and birds. Human infection results primarily from mosquito bites; blood transfusion, organ transplantation, breast feeding and in utero or occupational exposure have all been associated with viral infection (2002a; 2002b; Alpert et al., 2003; Charatan, 2002). Although most WNV infections in humans are asymptomatic, severe neurological disease (including encephalitis) and death have been observed with a higher frequency in the elderly and immunocompromised (Campbell et al., 2002; Pletnev et al., 2006). Recent evidence also suggests that WNV can persist for years in humans and animals convalescing from infection (Appler et al., 2010; Murray et al., 2010; Tesh et al., 2005). Currently, licensed vaccines are not yet ready to use in humans. Treatment is currently nonspecific and supportive (Campbell et al., 2002). WNV has been studied in various animal models, including mice, hamsters, monkeys and horses (Davis et al., 2001; Kramer & Bernard, 2001; Ratterree et al., 2004; Xiao et al.,