title: Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor.
abstract: Interferons (IFNs) are a family of multifunctional cytokines with antiviral activities. The K9 open reading frame of Kaposi's sarcoma-associated herpesvirus (KSHV) exhibits significant homology with cellular IFN regulatory factors (IRFs). We have investigated the functional consequence of K9 expression in IFN-mediated signal transduction. Expression of K9 dramatically repressed transcriptional activation induced by IFN-alpha, -beta, and -gamma. Further, it induced transformation of NIH 3T3 cells, resulting in morphologic changes, focus formation, and growth in reduced-serum conditions. The expression of antisense K9 in KSHV-infected BCBL-1 cells consistently increased IFN-mediated transcriptional activation but drastically decreased the expression of certain KSHV genes. Thus, the K9 gene of KSHV encodes the first virus-encoded IRF (v-IRF) which functions as a repressor for cellular IFN-mediated signal transduction. In addition, v-IRF likely plays an important role in regulating KSHV gene expression. These results suggest that KSHV employs an unique mechanism to antagonize IFN-mediated antiviral activity by harboring a functional v-IRF.
authors.affiliation: New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: F
authors.initials: F
authors.lastname: Neipel
authors.forename: B
authors.initials: B
authors.lastname: Fleckenstein
authors.forename: K
authors.initials: K
authors.lastname: Ozato
authors.forename: J U
authors.initials: JU
authors.lastname: Jung
mesh_terms: D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000502:physiology*; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D010750:Phosphoproteins / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014764:Viral Proteins; D007372:Interferons