Bovine viral diarrhoea virus and bovine herpesvirus-1 prime uninfected macrophages for lipopolysaccharide-triggered apoptosis by interferon-dependent and -independent pathways.
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 (M&phi;) infected 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 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 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 herpesvirus-1 are shown to contain such priming activity. Two lines of evidence indicate that factors in addition to IFN type I prime uninfected M&phi; for apoptosis. First, supernatants of M&phi; 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.
Perler
L
L
Institute of Veterinary Virology, University of Berne, Laenggass-Str. 122, CH-3012 Berne, Switzerland.
Schweizer
M
M
Jungi
T W
TW
Peterhans
E
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001912:Bovine Virus Diarrhea-Mucosal Disease; D002417:Cattle; D002450:Cell Communication; D002478:Cells, Cultured; D007242:Herpesvirus 1, Bovine; D007372:Interferons / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000473:pathology* / Q000502:physiology / Q000821:virology*; D008969:Molecular Sequence Data
D008070:Lipopolysaccharides; D007372:Interferons