title: Human T-cell leukemia virus type 1 blunts signaling by interferon alpha.
abstract: Although many animal viruses block the interferon (IFN) signaling pathway, this issue has not been previously investigated in retrovirus-infected cells. For this purpose, an infectious molecular clone of human T-cell leukemia virus type 1 (HTLV-1) was transfected into 293T or HeLa cells and was found to reduce interferon-stimulated response element (ISRE) reporter activity. This effect was independent of expression of the polymerase or envelope products and independent of the ability of Tax to activate the NFkappaB transcriptional pathway. IFN-alpha activation of 6 of 7 endogenous ISRE-regulated genes was also variably reduced, but not IFN-gamma-activated response element-mediated expression of interferon regulatory factor 1. HTLV-1 reduced the phosphorylation of tyrosine kinase 2 (TYK2) and signal transducer and transcriptional activator 2 (STAT2), suggesting a specific effect of HTLV-1 on the ability of an adaptor tyrosine kinase to transfer an IFN signal to the STAT-transcriptional activator complex.
authors.affiliation: Division of Molecular Oncology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Feng
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
mesh_terms: D002460:Cell Line; D017930:Genes, Reporter; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008954:Models, Biological; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D050795:STAT2 Transcription Factor / Q000378:metabolism; D053634:TYK2 Kinase / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D008156:Luciferases; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase; C070139:TYK2 protein, human