title: Host defense, viruses and apoptosis.
abstract: To thwart viral infection, the host has developed a formidable and integrated defense network that comprises our innate and adaptive immune response. In recent years, it has become clear that in an attempt to prevent viral replication, viral dissemination or persistent viral infection of the cell, many of these protective measures actually involve the induction of programmed cell death, or apoptosis. An initial response to viral infection primarily involves the innate arm of immunity and the killing of infected cells with cytotoxic lymphocytes such as natural killer (NK) cells through mechanisms that include the employment of perforin and granzymes. Once the virus has invaded the cell, however, a second host defense-mediated response is also triggered which involves the induction of a family of cytokines known as the interferons (IFNs). The IFNs, which are essential for initiating and coordinating a successful antiviral response, function by stimulating the adaptive arm of immunity involving cytotoxic T cells (CTLs), and by inducing a number of intracellular genes that directly prevent virus replication/cytolysis or that facilitate apoptosis. The IFN-induced gene family is now known to comprise the death ligand TRAIL, the dsRNA-dependent protein kinase (PKR), interferon regulatory factors (IRFs) and the promyelocytic leukemia gene (PML), all of which have been reported to be mediators of cell death. That DNA array analyses indicate that numerous cellular genes, many as yet uncharacterized, may similarly be induced by IFN, further emphasizes the likely importance that these cytokines have in the modulation of apoptosis. This likelihood is additionally underlined by the elaborate strategies developed by viruses to inhibit IFN-antiviral function and the mechanisms of cell death.
authors: Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, FL 33136, USA. gbarber@med.miami.edu
authors: G N
authors: GN
authors: Barber
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D004722:Endoribonucleases / Q000378:metabolism; D005809:Genes, Regulator / Q000235:genetics / Q000502:physiology; D006801:Humans; D007372:Interferons / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D009687:Nuclear Proteins; D009843:Oligoribonucleotides / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D012330:RNA, Double-Stranded / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014777:Virus Diseases / Q000276:immunology*; D014780:Viruses / Q000378:metabolism* / Q000472:pathogenicity; D019892:eIF-2 Kinase / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000227:Adenine Nucleotides; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009843:Oligoribonucleotides; D000071156:Promyelocytic Leukemia Protein; D012330:RNA, Double-Stranded; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D019014:fas Receptor; C070576:PML protein, human; C023505:2',5'-oligoadenylate; D007372:Interferons; D019892:eIF-2 Kinase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease