Micro-thermostat controls infection tied to common AIDS cancer
SAN ANTONIO (Jan. 19, 2010) — A tiny molecule called a microRNA acts as a thermostat regulating infection by the Kaposi’s sarcoma-associated herpesvirus, researchers at The University of Texas Health Science Center at San Antonio reported this week in Nature Cell Biology.
Kaposi’s sarcoma-associated herpesvirus is linked to a number of malignant cancers seen in AIDS patients, including the most common and deadly, Kaposi’s sarcoma. In AIDS-riddled Africa, Kaposi’s sarcoma represents 20 percent to 40 percent of all cancers in some locations.
The molecular thermostat is made by the virus itself. It either slows viral replication to allow the virus to hide out in the body — thereby evading the immune system — or speeds up replication as the virus mounts an offensive, said Shou-Jiang (S.J.) Gao, Ph.D., the H-E-B Distinguished Chair for Cancer Research at the Health Science Center.
“Almost every herpesvirus makes multiple microRNAs,” Dr. Gao said. “We have barely scratched the surface about how they affect viral replication and infect cells. Our paper is the first to use a genetic approach to show that a microRNA regulates the viral lifecycle of Kaposi’s sarcoma-associated herpesvirus.”
The viral microRNA influences NF-κB, a protein complex that plays a crucial role in the immune response to inflammation, said Dr. Gao, a professor in the School of Medicine and the Graduate School of Biomedical Sciences at the Health Science Center. He heads the tumor virology program at the university’s Greehey Children’s Cancer Research Institute.
The NF-κB connection is intriguing because the inflammatory activities of this protein complex are very important for cancer progression and spread, Dr. Gao said. Up to one-fifth of cancers are caused by viral infections.
The first microRNA was discovered in 1993 in a nematode worm. As the name microRNA indicates, it is a snippet of RNA, a molecule that reads and executes DNA commands. DNA is the genetic blueprint in cells.
Dr. Gao is also a virology researcher for the Cancer Therapy & Research Center at the UT Health Science Center. Study investigators include Drs. Xiufen Lei, Zhiqiang Bai, Jianping Xie, Fengchun Ye and Changil Kim. Dr. Yufei Huang from The University of Texas at San Antonio is a collaborator.
Nature Cell Biology made the study available on its Web site in advance online publication. An abstract is available without subscription at http://dx.doi.org/10.1038/ncb2019.
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