P&S Journal: Winter 1997, Vol.17, No.1
Researchers Confirm Herpesvirus Role in KS
Two new studies from P&S researchers have effectively ended a two-year controversy over the role of Kaposi's sarcoma-associated herpesvirus (KSHV) in Kaposi's sarcoma. The studies, published in the New England Journal of Medicine and Nature Medicine, used two versions of a newly developed assay to search for KSHV antibodies in groups at high and low risk for KS.
In the study reported in the New England Journal of Medicine, Dr. Shou-Jiang Gao, lead author and research scientist, and Dr. Patrick S. Moore, associate professor, both in the epidemiology department of the School of Public Health, and Dr. Yuan Chang, assistant professor of pathology at P&S, used an immunoblot assay to test blood samples of 40 HIV-positive gay men, all of whom later developed KS. (The researchers used data gathered in the Multicenter AIDS Cohort Study.) The samples, which were taken over periods ranging from six months to eight years, showed that only 11 of the men were positive for KSHV when first tested. Instead, most of the samples--from 21 individuals--began as negative and converted to positive for KSHV. Eight samples either remained negative or converted from positive to negative.
Sensitivity of the assay remains an important issue. A control group of 122 blood donors at low risk for KS turned up no positive tests for KSHV.
In the study reported in Nature Medicine, researchers used an immunofluoresence assay to search for KSHV in blood donors in the United States and Italy and in cancer patients in Uganda. None of the U.S. blood donors were positive; 4 percent of the Italian subjects had positive results. KSHV infection was more common among the Ugandans, with 51 percent testing positive. Uganda has the highest rate of KS infection in the world.
These results indicate that KSHV is most likely the cause of KS, says Dr. Moore. "This is essentially the last nail in the coffin for proving causality. In my mind there is no question that KSHV causes KS." Drs. Moore and Chang first identified herpesvirus-like DNA sequences in KS lesions of AIDS patients in 1994 (Science, Volume 266, p. 1865). Since that time some experts have argued that KSHV infection is common and does not cause KS. But, says Dr. Moore, viruses that are ubiquitous, such as Epstein-Barr virus, circulate explosively during childhood so that most people are seropositive by the time they are adults. These studies show that KSHV does not follow this pattern, although researchers still need to conduct more tests to get a true rate of infection in the general population.
The study has several implications. First, says Dr. Moore, this antibody assay in effect predicts the eventual development of a cancer. "This is a new human tumor virus," he says. "If we can understand its mechanisms we may then be able to design better ways to treat the cancer." The study also emphasizes the need for HIV-positive individuals to maintain safe sex practices, since many of the gay men in the study were infected by KSHV after they became HIV-positive. "Kaposi's sarcoma is a painful, disfiguring, and debilitating disease that may exacerbate the symptoms of AIDS and often results in death," says Dr. Moore.
The researchers plan to concentrate on increasing the sensitivity of the assays, which now detect the presence of KSHV antibodies 80 percent to 90 percent of the time.
Funding for the research came from several sources: the Centers for Disease Control and Prevention, the NIH, a James McDonnell Scholar Award, and the Istituto Superiore di Sanita, Roma.