Development of a Cell Culture System for HIV Infection

Hepatitis E virus (HEV) is the major etiologic agent for enterically transmitted non-A, non-Bhepatitis. Hepatitis E represents more than half of the acute viral hepatitis cases occurring in developingcountries where large epidemics affect young to middle-aged adults. Systematic studies on HEVreplication and pathogenesis are needed to guide diagnosis and prevention. No current method isavailable to grow HEV in culture. Our goal is to identify an in vitro infectious HEV molecule and toestablish a cell culture system amenable to supporting viral replication. A full-length cDNA clone andin vitro-synthesized RNA transcripts of HEV will be tested for their respective abilities to infectsusceptible cells in culture. To confirm in vitro infection, we will examine RNA- and DNA-transfectedcells for the presence of replicative RNA species as well as authentic viral proteins. With theestablishment of a cell culture system for HEV infection, we will, in future phase studies, investigate itspotential utilities to provide useful reagents for the development of diagnostics and vaccine. It will alsoprovide a model to study HEV cellular pathogenesis and, thus, potential ways to interfere with theprocess.