Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis

Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family , is an economically important cattle pathogen with a worldwide distributio n. Both noncytopathic (ncp) and cytopathic (cp) biotypes of BVDV can be iso lated from persistently infected cattle suffering from the lethal mucosal d isease. The cp biotype correlates with the production of the NS3 nonstructu ral protein, which in the corresponding ncp biotype is present in its uncle aved form, NS23, Previously, we have shown that cp hut not ncp BVDV induces the formation of aip interferons in bovine macrophages. In this study, we demonstrate that ncp BVDV inhibits the induction of apoptosis and the expre ssion of interferon alpha/beta by poly(IC), a synthetic double-stranded RNA (dsRNA). Inhibition was observed only in cells which had been infected wit h ncp BVDV at least 12 h prior to the addition of dsRNA, which indicates th at expression of viral proteins is necessary for the ncp virus to inhibit t he effects of poly(IC), Additional experiments using transfected poly(IC) s howed that ncp BVDV interfered with the intracellular action of dsRNA rathe r than with its uptake into the cells. Infected cells were not resistant to induction of apoptosis by actinomycin D or staurosporine, which suggests t hat ncp BVDV may specifically interfere with signaling through dsRNA, Inter ference with the innate antiviral host responses may explain the successful establishment of persistent infection by ncp BVDV in fetuses early in thei r development.