J Virol. which is important in the establishment of JEV persistence. A variety of animal DNA and RNA viruses can establish long-term persistent infections. For a cytolytic virus to SJ572403 institute a persistent infection in its host cells, more harmonious interactions between virus and cell must first occur to restrict the virus-induced cytopathic effects (CPE). This persistent status can be achieved by virus infection of nonpermissive cells or of cells under a nonpermissive environment; alternatively, emergence of virus and/or cell variants during the infection course appears to also contribute to persistence (3). True latent infections, which do not yield infectious virions, are commonly associated with DNA viruses when nonpermissive cells are infected; the virus may resume replication as long as the condition remains appropriate. On the other hand, the lack of susceptibility of target cells to virus infection often leads to an abortive replication of RNA viruses. Most RNA viruses can only persist in infected cells where at minimum a reduced level of virus replication is still able to take place, thereby resulting in constant shedding of moderate Rabbit polyclonal to PNPLA8 amounts of infectious virions. Characteristically, most animal DNA viruses seem to merely play a passive role either in the establishment of latency or in viral reactivation (reviewed in reference 3). In contrast, both viruses and their infected host cells have been shown to actively participate in the establishment of persistence for several RNA viruses, namely reovirus (2), Sindbis virus (25), poliovirus (1, 54), and coxsackie A9 virus (50). Among these viruses, mutations in certain viral genes have been demonstrated to be responsible for turning a lytic infection into a persistent one (reviewed in reference 3). Still, the involvement of cellular genes in viral persistence remains largely unexplored. Human was the first cellular gene recognized to be capable of blocking apoptosis induced by certain RNA viruses (21, 26, 27, 39, 51). Studies involving Sindbis SJ572403 virus (26), Semiliki Forest virus (44), and influenza virus (21, 38) have further indicated that constitutive expression can not only prevent the infected cells from undergoing apoptosis but also, subsequently, render the cells to be persistently infected. These results suggest that may play a role in determining whether a cytolytic RNA virus can chronically infect its host cells. Like other mosquito-borne flaviviruses, Japanese encephalitis virus (JEV) is transmitted to humans through persistently infected mosquito vectors. JEV infection is especially prevalent in some East Asian countries and may cause an acute encephalitis in humans which is frequently associated with a high mortality rate (6, 52, 53). The genome of JEV is a single-stranded, positive-sense RNA of approximately 11 kb in length which contains an open reading frame encoding a single polyprotein. In the infected cells this viral SJ572403 polyprotein is proteolytically cleaved into at least 11 proteins. The virus structural proteins, including the capsid (C), membrane (M; precursor M, prM), and envelope (E) proteins, are encoded by the 5 one-third of the open reading frame, and the nonstructural (NS) proteins, designated NS1 through NS5, are encoded in the remainder (reviewed in references 10 and 42). Among these proteins, prM, E, and NS1 are membrane-associated glycoproteins. With two N-linked glycosylation sites at amino acid positions 130 and 207, the actual molecular size of NS1 detected in JEV-infected cells is approximately 46 kDa. The proteolytic cleavage between E-NS1 ensues the translocation of NS1 into the lumen SJ572403 SJ572403 of the endoplasmic reticulum (ER), and the cleavage between NS1-2A might occur in the lumen of the vesicular compartments (10). JEV is unique among flaviviruses in that an additional NS1-2A-related protein (named NS1) with a molecular size of about 53 kDa is often observed in the JEV-infected cells (10) and is probably generated by an unknown protease that recognizes an alternative cleavage site within NS2A (32). The biological significance for the existence of both types of NS1 proteins in JEV-infected cells remains unclear. The natural life cycle of JEV involves complex relationships among arthropods, vertebrate reservoirs, and humans, illustrating the uniqueness of the broad host spectrum for JEV infection (9). In fact, a wide variety of primary and continuous cell cultures from different origins (e.g., monkey, hamster, pig, chicken, and mosquito).