Kaposi's sarcoma-associated herpesvirus-encoded oncogenes and oncogenesis.
Molecular biologic studies of Kaposi's sarcoma-associated herpesvirus (KSHV) have identified a number of potential viral oncogenes that may contribute to KSHV-related neoplasia including a D-type cyclin, an IL-6-like cytokine, and a novel member of the interferon regulatory factor family. KSHV is functionally related to other DNA tumor viruses by encoding specific proteins to inhibit pRb, pro-apoptotic, and interferon-signaling tumor suppressor pathways. The virus appears to employ molecular piracy of cellular regulatory genes as a mechanism to avoid cellular antiviral responses. The transparency of the KSHV genome allows ready identification of the cellular regulatory pathways which may be involved in transformation by KSHV. This provides strong support to the notion that some tumor suppressor pathways serve the dual function of being antiviral pathways to induce cell cycle arrest, apoptosis, and enhanced cell-mediated immunity in response to virus infection. Neoplasia may result from specific viral strategies to overcome these host defense pathways.
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
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Moore
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Chang
D016679:Genome, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D012514:Sarcoma, Kaposi / Q000821:virology*