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Attack of the clones

Deadly Kaposi's sarcoma virus meets its match at UTHSC

San Antonio (Sept. 22, 2003) — Scientists at The University of Texas Health Science Center at San Antonio (UTHSC) are believed to be the first in the world to have successfully cloned the virus that causes Kaposi's sarcoma, a deadly cancer most commonly seen in patients with AIDS. In addition, they have developed what is called a "shuttle system" for studying the cancer-causing traits of the Kaposi's sarcoma-associated herpesvirus (KSHV), thus providing the first successful method for studying why and how KSHV causes cancer. Their research is in the September 2003 issue of the Journal of Virology.

The National Cancer Institute of the National Institutes of Health (NIH) awarded Shou-Jiang Gao, Ph.D., an associate professor in the departments of pediatrics, medicine, and microbiology and immunology at UTHSC, a $1.6 million grant over five years for his research. Scientists from England, Germany, Italy and more than 20 U.S. research institutions are lining up to collaborate with Dr. Gao and his team on this breakthrough.

KSHV, as with all herpesviruses, is a shrewd virus. It can lie dormant in its host for several years, waiting for the right moment when the host's immune system becomes weak. Then it attacks, transforming normal cells into cancer cells that wreak havoc on body tissues. The result is Kaposi's sarcoma — a disfiguring rash of purplish, often painful lesions that grow in the mouth and on the skin. In more aggressive cases, Kaposi's sarcoma damages internal organs such as the lungs, lymph nodes and digestive tract, often proving fatal. In the last 20 years, the vast majority of Kaposi's sarcoma cases have developed in patients with acquired immunodeficiency syndrome (AIDS).

Dr. Gao and his colleagues are working with blood and tissue centers to study the KSHV infection rate in Texas. They found that 15 percent of blood donor samples studied in Texas were infected, as compared to 5 percent to 12 percent in other parts of the country. Studies also revealed a higher rate of specific strains of KSHV in Hispanic Kaposi's sarcoma patients in South Texas. Health experts are concerned that these figures raise the possibility that KSHV could be transmitted through blood transfusions during routine operations. Dr. Gao and his team received a grant of nearly $1 million from the NIH for this aspect of their research.

Dr. Gao also is on a mission to find the cancer-causing genes of the virus. That's where his "shuttle system" comes in. His shuttle consists of the cloned KSHV in a Bacterial Artificial Chromosome (BAC), which is like an incubator that allows the virus to grow in bacteria. The BAC serves as a mini-transporter that shuttles the virus from the bacteria into human cells and vice versa. When the virus is in the bacteria, Dr. Gao can manipulate it. In a much quicker fashion than it took him to assemble it, he begins to disassemble the cloned KSHV, pulling its proteins, or genes, apart. Then he shuttles the mutated virus back into the human cells. Using the latest molecular biology technology, he watches closely to see how each gene reacts among the human cells, waiting for signs of infection and emergence of cancer cells.

With more than 90 genes in the KSHV to study, Dr. Gao has his work cut out for him. But he is persistent and won't quit until he discovers the combination of KSHV genes that causes cancer in human cells. Once he does, researchers across the country will be able to work on developing vaccines and drugs that target KSHV.

In essence, Dr. Gao is using a virus clone to attack and defeat itself — the recipe for an exciting science fiction novel — except that this scenario is real, with the potential to save thousands of lives.

Contact: Natalie Gutierrez or Will Sansom