title: Loss of (2'-5')oligoadenylate synthetase activity by production of antisense RNA results in lack of protection by interferon from viral infections.
abstract: An expression vector was constructed that carries part of the human BK papovavirus with 0.5 kilobases of (2'-5')oligoadenylate (2-5A) synthetase cDNA inserted in inverted orientation downstream from the virion proteins (VP) promoter and the neomycin-resistance gene neo under the control of a simian virus 40 promoter. Cells transfected with this vector and selected for resistance to the neomycin derivative G418 synthesized RNA complementary to 2-5A synthetase mRNA. These cells lacked 2-5A synthetase activity, and the enzyme was not inducible by interferon. In contrast, 2-5A synthetase was induced in cells transfected with a control vector without the cDNA insert. Such cells were protected by interferon from RNA viruses, whereas cells lacking 2-5A synthetase were not protected from encephalomyocarditis virus, vesicular stomatitis virus, and Sindbis virus but were fully protected from influenza virus. These findings show that a high level of 2-5A synthetase is required for interferon-induced protection from the cytoplasmic RNA viruses tested.
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D001739:BK Virus / Q000201:enzymology / Q000235:genetics*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D012516:Osteosarcoma; D011120:Polyomavirus / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D018075:RNA, Complementary; D013045:Species Specificity; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014780:Viruses / Q000187:drug effects
chemical_list: D007370:Interferon Type I; D018075:RNA, Complementary; D012313:RNA; D004247:DNA; D015088:2',5'-Oligoadenylate Synthetase