Effects of viral inhibitors of apoptosis in models of mammalian cell death.

Apoptotic cell death is used as a defence against infection by viruses. To counter this protective mechanism, some viruses carry genes whose products can inhibit progression of the apoptotic process in the host cell. As it is clear that the core cell death mechanisms have been conserved through evolution, viral genes from various sources can be used to unravel these mechanisms in mammalian cells. We have produced transgenic mice that express the cowpox gene crmA in their T cell compartment, and analysed their susceptibility to apoptosis. We have studied the effects of the baculovirus genes p35 from Autographa californica nuclear polyhedrosis virus and IAP from Orgyia pseudotsugata nuclear polyhedrosis virus on cell death induced in HeLa cells by over-expression of interleukin-1 beta converting enzyme (ICE), overexpression of the CD95-associated protein FADD, or cell death induced by treatment with TNF plus cycloheximide. These experiments indicate that viral anti-apoptosis proteins target both the activation and effector phases of the physiological cell death process.