Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor.
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.
Li
M
M
New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Lee
H
H
Guo
J
J
Neipel
F
F
Fleckenstein
B
B
Ozato
K
K
Jung
J U
JU
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*
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