University of Pittsburgh Findings Illustrate How Kaposi's Sarcoma-Associated Herpesvirus Causes Cancer

Findings by researchers at the University of Pittsburgh Cancer Institute illustrate how Kaposi's sarcoma-associated herpesvirus 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.

Patrick S. Moore and Yuan Chang -- the team that previously discovered KSHV -- examined the expression of a virus-derived cytokine (a hormone-like substance that regulates cells during an immune response) in KSHV. Moore and Chang found that this cytokine, virus-derived interleukin-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 full report, "Viral IL-6-Induced Cell Proliferation and Immune Evasion of Interferon Activity," was published recently in Science (2002;298(5597):1432-1435).

vIL-6 inhibits the signaling of antiviral factor interferon (IFN), a normal immune response that blocks virus-infected cells from growing. However, KSHV has a built-in sensor mechanism that perceives an increased signaling of IFN and responds by increasing the production of vIL-6, in effect inhibiting the activation of the tumor-suppressor pathway during the immune response and acting like a switch by turning off the production of IFN. In addition, in some cells, vIL-6 not only stops the suppression of tumors, but also causes normal cells that are not infected with KSHV to proliferate abnormally.

"These results illustrate that tumor viruses can cause cancers because they have evolved to subvert cell defenses and make use of the same signaling pathways that are used to suppress tumors to instead cause tumors to grow," said Chang. "In other words, the virus is able to sense its environment and modify that environment to make it more habitable for the virus. By inhibiting a normal immune mechanism to evade the immune system, the virus can accidentally trigger tumor cell growth." Moore and Chang cautioned that this mechanism does not entirely explain how KSHV causes cancer, but it is an important principle in understanding tumor virology. Chang said vIL-6 may be a promising target for novel therapies against KSHV-associated tumors often found in lymphoma and Castleman disease, a rare disorder characterized by noncancerous tumors that may develop in the lymph node tissue throughout the body.

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