Human herpesvirus 8 encodes an interferon regulatory factor (IRF) homolog that represses IRF-1-mediated transcription.
Human herpesvirus 8 (HHV-8) is the probable viral etiologic agent for Kaposi's sarcoma. The HHV-8 genome encodes viral interferon regulatory factor (vIRF), a gene product that has homology to the IRF family of transcription factors. We demonstrate that vIRF inhibits responses to type I and type II interferons and blocks IRF-1-mediated transcription. vIRF does not compete with IRF-1 for binding to DNA or complex directly with IRF-1. The ability of vIRF to block IRF-1-mediated transcription is independent of the DNA binding domains of both vIRF and IRF-1. These data suggest that vIRF may contribute to viral pathogenesis and cellular transformation by interfering with interferon- and IRF-1-mediated gene expression through a novel mechanism.
Zimring
J C
JC
Winship Cancer Center, Emory University, Atlanta, Georgia 30322, USA.
Goodbourn
S
S
Offermann
M K
MK
D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000821:virology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology
D017931:DNA Primers; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D007370:Interferon Type I; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014764:Viral Proteins; D007371:Interferon-gamma