University of Pittsburgh findings published in Science illustrate how KSHV causes cancer

PITTSBURGH, Nov. 14 Findings published in this week's issue of the journal Science by researchers at the University of Pittsburgh Cancer Institute (UPCI) illustrate how the virus that causes Kaposi's sarcoma Kaposi's sarcoma-associated herpesvirus, or KSHV inhibits the body's immune response and causes cancer cells to grow through a technique called immune evasion. KSHV causes Kaposi's sarcoma, a cancer of the blood vessel cells that often occurs in tissues under the skin or mucous membranes, and is the most common malignancy occurring among AIDS patients. KSHV belongs to the family of herpesviruses that includes the causes of genital herpes, cold sores and chickenpox.

Patrick S. Moore, M.D., M.P.H., professor, department of molecular genetics and biochemistry, and Yuan Chang, M.D., professor, department of pathology the team who previously discovered KSHV examined the expression of a virus-derived cytokine (a hormone-like substance that regulates cells during an immune response) in KSHV. Dr. Moore and Dr. Chang found that this cytokine, viral IL-6 (vIL-6), not only inhibits immune function, but also causes cancerous cells to grow. vIL-6 protects virus-infected cells from undergoing growth arrest and apoptosis, or cell death, which is the normal way that the immune system attempts to limit viral infections.

"The importance of this finding is that it demonstrates that there is an overlap between the immune system and tumor suppressor pathways which are targeted by KSHV," said Dr. Moore, also director of the molecular virology program at UPCI. "It further demonstrates that viruses which inhibit immune functions also can, under some circumstances, induce tumor cells to grow because these viruses are attacking pathways that are important in both immunity and suppression of tumor growth."

Through a series of assays, the investigators examined how vIL-6 inhibits the signaling of antiviral factor interferon, or IFN. The signaling of IFN

Contact: Clare Collins
University of Pittsburgh Medical Center

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