Researchers pinpoint growth mechanism for cancer-related virus

SAN ANTONIO (May 20, 2011) — A team of researchers at The University of Texas Health Science Center at San Antonio has pinned down an important mechanism controlling the growth of Kaposi’s sarcoma-associated herpesvirus.

It eventually could mean that inexpensive antioxidants and anti-inflammatory drugs might potentially be used to prevent the flare-up of a type of cancer common in AIDS patients.

The discovery, published online Thursday in PLoS Pathogens, a top-ranked infectious disease journal, bodes well for the prevention and treatment of Kaposi’s sarcoma, said Shou-Jiang Gao, PhD, the H-E-B Distinguished Chair for Cancer Research and a professor in the School of Medicine at The University of Texas Health Science Center at San Antonio. That is especially true for patients in economically disadvantaged areas with high HIV infection rates, like sub-Saharan Africa.

“This is a limited laboratory and a mouse model study, so of course there is much more research to be done,” said Dr. Gao, the study’s lead investigator. “But it is certainly very promising.”

Dr. Gao has published several papers on Kaposi’s sarcoma-associated herpesvirus (KSHV), which is a risk factor for the cancer. After the initial infection, KSHV is latent in the body until it is reactivated. That reactivation contributes to the development of malignancies, including a type of lymphoma and Kaposi’s sarcoma, the most common cancer in untreated AIDS patients.

While different factors are known to reactivate the virus, until now the common mechanism controlling this process has been a mystery. Gao and his team show that the reactive oxygen species (ROS) hydrogen peroxide, a common factor produced during inflammation, stress and aging, as well as other physiological conditions such as diabetes, induces KSHV reactivation.

They also found that a common nutritional supplement, N-acetyl-L-cysteine (NAC) also effectively inhibits KSHV replication in mice with lymphoma, significantly prolonging their lifespan. And in a cell culture, KSHV’s growth was limited by NAC, as well as by a common enzyme called catalase and the antioxidant glutathione, all of which are capable of reducing the ROS level.

“The discovery of this novel mechanism of KSHV reactivation indicates that antioxidants and anti-inflammation drugs could be promising preventive and therapeutic agents in KSHV and its related malignancies,” Dr. Gao said.

Gao’s team includes Fengchun Ye, Ph.D.; Fuchun Zhou, Ph.D.; Xiufen Lei, M.D., Ph.D.; and Moraima Guadalupe, Ph.D., M.S.; as well as Roble G. Bedolla, M.D., M.S.C.I.; Tiffany Jones and Tao Kang.

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