Programmed cell death (apoptosis): its virological and immunological connections (a review).

Programmed cell death is a physiological, energy-consuming mechanism leading to suicide of the cell. Cell death is accomplished by the activation of endonucleases that fragment the cell's nuclear DNA. Some tumour cells remain susceptible to programmed death. These are hormone- and growth factor-dependent tumour cells. Hormone or growth factor deprivation induces signals leading to apoptosis. Other tumours gain strong resistance to apoptosis. One of the normal functions of the bcl-2 gene is to provide longevity to memory B cells. When this gene becomes translocated in follicular B cell lymphomas, it renders lymphoma cells resistant to apoptosis. Latent membrane protein encoded by an EBV gene, either by itself or by amplifying bcl-2, enables tumour cells (nasopharyngeal carcinoma; Reed-Sternberg cell of Hodgkin's disease) to resist apoptotic death. Loss of antioncogene p53 provides for resistance against programmed cell death. Breakdown of resistance to apoptosis in tumour cells can be achieved by oncolytic viruses; generation of lymphotoxin and tumour necrosis factor; monoclonal antibodies; transfection with plasmid vectors carrying p53; gamma irradiation; and certain chemotherapeutic agents.