The flavivirus bovine viral diarrhoea (BVD) virus exists in two biotypes, cytopathic (cp) and non-cytopathic (ncp), defined by their effect on cultured cells. Cp BVD virus-infected cells undergo apoptosis and may promote apoptosis in uninfected cells by an indirect mechanism. Macrophages (Mϕ) infected with cp, but not ncp, BVD virus release a factor(s) in the supernatant capable of priming uninfected Mϕ for activation-induced apoptosis in response to lipopolysaccharide. A possible role of interferon (IFN) type I was suggested previously by the observation that this cytokine primed for activation-induced apoptosis and was present in supernatants of Mϕ infected with cp, but not ncp, BVD virus. Here, supernatants of both Mϕ infected with a wider range of cp BVD virus and Mϕ infected with bovine herpesvirus-1 are shown to contain such priming activity. Two lines of evidence indicate that factors in addition to IFN type I prime uninfected Mϕ for apoptosis. First, supernatants of Mϕ infected with cp BVD virus contained much less IFN than is required for priming for apoptosis. Second, whereas antiviral activity was neutralized by a vaccinia virus-encoded IFN type I receptor, B18R, the capacity of the supernatant to prime for apoptosis was unaffected by this treatment. The apparent molecular mass of the factor(s) priming 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 virus replication.


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