title: Viral stress-inducible genes.
abstract: Virus-infection of mammalian cells causes transcriptional induction of many cellular genes, collectively called as "viral stress-inducible genes." The proteins encoded by these genes are essential to maintain cell-virus homeostasis, which is required for both virus replication and host survival. Many viral products, including RNA, DNA, and proteins, can induce these genes by using distinct, but partially overlapping, signaling pathways. Type I interferons, direct products of virus infection, can also induce many of these genes, thus providing a positive feedback loop. Double-stranded RNA, a common by-product of virus replication, can induce them by multiple signaling pathways initiated by Toll-like receptor 3 or RIG-I/Mda-5. Several viral stress-inducible proteins inhibit protein synthesis. Proteins of the P56 family bind to the translation initiation factor, eIF-3, and block translation initiation. PKR, a protein kinase, phosphorylates a different initiation factor, eIF-2, and inhibits translation initiation. However, unlike P56, PKR needs to be first activated by dsRNA or PACT, another cellular protein. Another family of enzymes, the 2'-5' oligoadenylate synthetases, synthesizes 2'-5' linked oligoadenylates [2-5(A)] in the presence of dsRNA; 2-5(A) activates the latent ribonuclease, RNase L, which degrades mRNA. Many viruses have evolved mechanisms to evade these genes by blocking their induction or actions; often more than one strategy is used by the same virus to achieve this goal. Thus, in an infected cell, equilibrium is reached between the virus and the cell with regards to the viral stress-inducible genes.
authors.affiliation: Department of Molecular Genetics, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Ganes C
authors.initials: GC
authors.lastname: Sen
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Peters
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D050810:Octamer Transcription Factors / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014777:Virus Diseases / Q000276:immunology* / Q000821:virology; D014780:Viruses / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D004268:DNA-Binding Proteins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D011506:Proteins; D016601:RNA-Binding Proteins; C115683:p56 oligoadenylate synthetase; D015088:2',5'-Oligoadenylate Synthetase