ABSTRACT
Rather than killing cells by toxic insult, most viruses trigger cells to activate the apoptotic death pathway, in which infected cells commit suicide. However, viruses have exploited a fascinating array of mechanisms to inhibit programmed cell death (Hardwick, 1998b). Different viruses tamper with cell suicide pathways by terminating cell death receptor signaling, mimicking cellular Bcl2 functions, and encoding protease inhibitors, among other tactics. These stealth strategies allow the virus to establish suitable environments for long-term persistence, for latency, or for progeny virus production. Other viruses, such as Sindbis virus, replicate efficiently in apoptotic cells, and apoptosis induced by these viruses can lead to disease (Levine et al., 1993; Ubol et al., 1994). Sindbis virus-induced apoptosis of neurons in the central nervous system of mice appears to be the cause of mortality in newborn mice (Lewis et al., 1996).
Sindbis virus infections are modulated by cellular apoptosis inhibitors, but little is known about the mechanisms that govern the relationship between a virus and its host. Nevertheless, investigation into viral strategies has significantly advanced our knowledge of cellular death pathways as well as viral pathogenesis and other disease states. We have established a model system using Sindbis virus as a vector to express cell death regulatory proteins. With this system, we can study the effects of these viral and cellular proteins that modulate programmed cell death and alter the outcome of a viral infection in animals.
