Susceptibility to cytotoxic T lymphocyte-induced apoptosis is a function of the proliferative status of the target

HSV-1 can induce the up-regulation of the immediate early (IE) transcription factor c-jun/AP-1 (c-jun) (28) . c-jun and c-fos are required for the serum-stimulated transition out of Go into G1 (29) . The c-jun-inducing activity was localized to the HSV-1 IE protein ICP0, which is rcqnired for the expression of IE proteins ICP4 and ICP27 (30) (31) (32) . ICP4 and ICP27 have been defined as containing immunodominant CTL epitopes in BALB/c mice (33, 34) . It is interesting to note that immunodominant MHC class I-restricted CTL epitopes have also been identified in the IE gene, pp89, of murine cytomegalovirus, which induces c-fos expression and cdlular DNA synthesis in host cells (35) . Thus, DNA viruses induce cdlular activation and replication competence through protooncogene expression, and DNA viral proteins synthesized early after infection may both induce cellular activation through protooncogene expression and provide CTL epitopes to render these unwanted cells susceptible to the full CTL armament. The earty recognition of the virus-infected cell by specific CTL could also allow for the degradation of viral DNA before viral packaging and release. Cell death by apoptosis is irreversible, but purified perforin has been shown to induce a transient membrane permeability that can be repaired (36) . Thus, the membrane lysis mechanism of CTL may be less efficient than the apoptosis mechanism for irreversible killing of a target, and the induction of competence for CTLinduced apoptosis may therefore be of pathological significance.