Host defense, viruses and apoptosis

To thwart viral infection, the host has developed a formidable and integrat ed defense network that comprises our innate and adaptive immune response. In recent years, it has become clear that in an attempt to prevent viral re plication, viral dissemination or persistent viral infection of the cell, m any of these protective measures actually involve the induction of programm ed cell death, or apoptosis, An initial response to viral infection primari ly involves the innate arm of immunity and the killing of infected cells wi th cytotoxic lymphocytes such as natural killer (NK) cells through mechanis ms that include the employment of perforin and granzymes, Once the virus ha s invaded the cell, however, a second host defense-mediated response is als o triggered which involves the induction of a family of cytokines known as the interferons (IFNs), The IFNs, which are essential for initiating and co ordinating a successful antiviral response, function by stimulating the ada ptive arm of immunity involving cytotoxic T cells (CTLs), and by inducing a number of intracellular genes that directly prevent virus replication/cyto lysis or that facilitate apoptosis, The IFN-induced gene family is now know n to comprise the death ligand TRAIL, the dsRNA-dependent protein kinase (P KR), interferon regulatory factors (IRFs) and the promyelocytic leukemia ge ne (PML), all of which have been reported to be mediators of cell death. Th at DNA array analyses indicate that numerous cellular genes, many as yet un characterized, may similarly be induced by IFN, further emphasizes the like ly importance that these cytokines have in the modulation of apoptosis, Thi s likelihood is additionally underlined by the elaborate strategies develop ed by viruses to inhibit IFN-antiviral function and the mechanisms of cell death.