Auto-activation of the transforming viral interferon regulatory factor encoded by Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8).
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 cis elements, named Vac1 and Vac2, in the vIRF promoter that were responsive to vIRF activation. vIRF auto-activation via Vac1 but not Vac2 was repressed by Tis, a transcriptional silencer in the vIRF promoter. Neither Vac1 nor Vac2 contain any interferon-stimulated response element (ISRE)-like sequences and are unresponsive to induction with interferon-beta and -gamma. 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.
Wang
Xin-Ping
XP
Departments of Pediatrics, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.|Tumor Virology Program, Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Gao
Shou-Jiang
SJ
Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.|Departments of Pediatrics, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.|San Antonio Cancer Institute, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.|Microbiology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.|Tumor Virology Program, Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D050835:Interferon Regulatory Factors; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014764:Viral Proteins
D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D014157:Transcription Factors; D014764:Viral Proteins; C413486:viral interferon regulatory factors