Bovine viral diarrhoea virus and bovine herpesvirus-1 prime uninfected macrophages for lipopolysaccharide-triggered apoptosis by interferon-dependentand -independent pathways

The flavivirus bovine viral diarrhoea (BVD) virus exists in two biotypes, c ytopathic (cp) and noncytopathic (ncp), defined by their effect on cultured cells, Cp BVD virus-infected cells undergo apoptosis and may promote apopt osis in uninfected cells by an indirect mechanism. Macrophages (M phi) infe cted with cp, but not ncp, BVD virus release a factor(s) in the supernatant capable of priming uninfected M phi for activation-induced apoptosis in re sponse to lipopolysaccharide, A possible role of interferon (IFN) type I wa s suggested previously by the observation that this cytokine primed for act ivation-induced apoptosis and was present in supernatants of M phi infected with cp, but not ncp, BVD virus. Here, supernatants of both M phi infected with a wider range of cp BVD virus and M phi infected with bovine herpesvi rus-l are shown to contain such priming activity, Two lines of evidence ind icate that factors in addition to IFN type I prime uninfected M phi for apo ptosis, First, supernatants of M phi infected with cp BVD virus contained m uch less IFN than is required for priming for apoptosis, Second, whereas an tiviral activity was neutralized by a vaccinia virus-encoded IFN type I rec eptor, B18R, the capacity of the supernatant to prime for apoptosis was una ffected by this treatment. The apparent molecular mass of the factor(s) pri ming for apoptosis was between 30 and 100 kDa, Priming of uninfected cells for activation-induced apoptosis may add a new facet to virus pathogenesis and may contribute to the formation of lesions not related directly to viru s replication.