Sarah Goodwin

Kathi Ovnic
Holly Korschun
Emory Cancer Researcher Studies Virus Linking AIDS, Kaposi's Sarcoma

An Emory cancer researcher has found the virus that causes Kaposi's sarcoma may also prevent medication used to treat the disease from working.

Kaposi's sarcoma (KS) was considered a rare cancer prior to the early 1980s, when it began to appear as an infection associated with the AIDS virus. While people without AIDS can develop KS, the incidence is at least 20,000 times greater, and may be up to 70,000 times greater, in AIDS patients. New research has shown that although KS is not caused by HIV, the virus that causes KS may be activated by the AIDS virus.

Human herpesvirus 8 (HHV8) is a recently discovered member of the herpes family. Like other herpes viruses, HHV8 may lie dormant for life, and as much as 20% of the population may carry it without ever being affected. Margaret "Kenny" Offermann, MD, PhD, a cancer physician and researcher, has focused much of her work since the 1994 discovery of HHV8 on its relationship to KS. Offermann and her team reported earlier this year in the Journal of Virology that the HHV8 gene product viral interferon regulatory factor, or vIRF, blocks the ability of the cells to respond to interferon, one of the main defenses used by the body to fight viral infection and tumor development and a therapy used in treating KS patients.

"We're studying the expression of vIRF, including what turns it on and off, how it interferes with interferon response, how it leads to malignant transformation, how it affects the viral life cycle," Offermann says.

Offermann suspects that an HIV-encoded protein may activate HHV8, which then expresses vIRF and other viral proteins, contributing to the malignant transformation in AIDS patients.

"There are two different scenarios by which HIV could contribute to the development of KS," Offermann says. "One is that the host response to the AIDS virus can lead to some changes that will induce mutations in the genome and will allow cells to survive and to accumulate the necessary number of mistakes to become malignant. Estimates are that you need at least five mutations in tumor suppresser genes and oncogenes to get a frank malignancy, and a number of viruses can help those mutations occur." The other scenario is that cancer viruses bring in genetic material that affects the programming of the cell and allows malignancy to develop. Offermann says in the case of HHV8, it is probably a combination of both, but HHV8 is clearly bringing material into the cell.

Offermann and her team are working on a study with the Centers for Disease Control and Prevention to collect clinical samples of KS. With a larger data pool, Offermann wants to address what happens when patients are treated for KS at the same time they are treated for AIDS. She is looking at changes in expression of both cellular and viral genes to begin to understand some of the events that actually lead to the progression or control of the disease. Results of Offermann's research are not limited to HHV8.

"When we began this work the number of examples of viruses that were associated with human cancers were relatively limited," Offermann says. "The number of viruses that are associated with cancer keeps going up, and recent estimates have suggested that about 30% of human cancers have some sort of viral link."