A cellular J-domain protein modulates polyprotein processing and cytopathogenicity of a pestivirus

Pestiviruses are positive-strand RNA viruses closely related to human hepat itis C virus. Gene expression of these viruses occurs via translation of a polyprotein, which is further processed by cellular and viral proteases. He re we report the formation of a stable complex between an as-yet-undescribe d cellular J-domain protein, a member of the DnaJ-chaperone family, and pes tiviral nonstructural protein NS2. Accordingly, we termed the cellular prot ein Jiv, for J-domain protein interacting with viral protein. Jiv has the p otential to induce in trans one specific processing step in the viral polyp rotein, namely, cleavage of NS2-3. Efficient generation of its cleavage pro duct NS3 has previously been shown to be obligatory for the cytopathogenici ty of the pestiviruses. Regulated expression of Jiv in cells infected with noncytopathogenic bovine viral diarrhea virus disclosed a direct correlatio n between the intracellular level of Jiv, the extent of NS2-3 cleavage, and pestiviral cytopathogenicity.