1887

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus-8-encoded viral interferon regulatory factor (vIRF) transforms NIH3T3 cells, represses interferon signal transduction and regulates the expression of other KSHV genes. Here, we have shown that vIRF is a transcriptional activator and auto-activates its own expression. Ectopic expression of vIRF activated the vIRF promoter in KSHV-negative 293, COS7, HeLa and BJAB cell lines in a dose-dependent fashion in a reporter assay and the expression of vIRF transcripts from endogenous viral genomes in BCBL-1 and BC-1 cells latently infected with KSHV. Deletion analysis identified two elements, named and , in the vIRF promoter that were responsive to vIRF activation. vIRF auto-activation via but not was repressed by , a transcriptional silencer in the vIRF promoter. Neither nor contain any interferon-stimulated response element (ISRE)-like sequences and are unresponsive to induction with interferon-β and -γ. These results indicate that KSHV uses the mechanism of auto-activation to regulate the expression of a viral transforming protein to efficiently evade host tumour suppressor pathways.

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2003-02-01
2019-12-06
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