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 direc tly with IRF-1. The ability of vIRF to block IRF-1-mediated transcript ion 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-medi ated gene expression through a novel mechanism.