Apoptosis is the process whereby individual cells of multicellular organisms undergo systematic self-destruction in response to a wide variety of stimuli. Apoptosis is a genetically controlled preprogrammed event which eliminates cells during development when they have become redundant or which functions as an emergency response after radiation damage, viral infection, or aberrant growth induced by the activation of oncogenes. In the case of virus-infected cells, the induction of early cell death would severely limit virus production and reduce or eliminate spread of progeny virus in the host. Thus, most animal viruses have evolved strategies to evade or delay early apoptosis to allow production of high yields of progeny virus. Over the past few years both the biochemical basis of apoptosis and its regulation by viral products have become clearer. For example, part of the apoptotic program includes the induction of cellular endonucleases which could target replicating viral DNA and prevent virus production at a very early stage. Thus, the problem facing the virus is to replicate and package large numbers of progeny genomes safely within newly synthesized viral capsids. Many viruses have evolved genes encoding proteins which effectively suppress or delay apoptosis long enough for the production of sufficient quantities of progeny. In addition, a growing number of viruses are now known to induce apoptosis actively at late stages of infection. This process may represent a final and important step in the spread of progeny to neighboring cells while also evading host immune inffammatory responses and protecting progeny virus from host enzymes and antibodies. Such virally induced apoptosis may also contribute to some clinical manifestations and cytotoxicity associated with several human diseases of viral origin.

The purpose of this review is to summarize recent information on the induction and suppression of apoptosis by viral products as well as to propose how this knowledge may provide insights into basic cell biology and offer the potential of new therapeutic applications. A recent comprehensive review by Shen and Shenk (75) also deals with some aspects of the subjects covered below.