April 2001

From University of Pittsburgh Medical Center

Kaposiís sarcoma-associated herpesvirus causes no negative health effects in hiv-negative individuals, find University of Pittsburgh researchers

PITTSBURGH, April 9 Ė New research at the University of Pittsburgh shows that a recently discovered herpesvirus, which often leads to Kaposiís sarcoma in HIV-positive individuals, has no negative effect on healthy HIV-negative adults. The study is published in the April 15 issue of Blood, a journal of the American Society of Hematology.

Researchers at the Graduate School of Public Health found that human herpesvirus 8 (HHV8), often a precursor to the blood vessel cancer Kaposiís sarcoma (KS) in HIV-positive adults, causes no symptoms or only a mild flu-like illness in healthy adults without HIV, and has no negative effects on their immune systems.

"This is the first study to unravel the natural history of primary HHV8 infection in the absence of underlying HIV infection or organ transplantation," said lead author Charles Rinaldo, Ph.D., professor of pathology and infectious diseases and microbiology. "Knowing how HIV-negative, otherwise healthy individuals respond to this virus in terms of symptoms and immune responses is important in preventing related diseases."

In a previous study, Dr. Rinaldo showed that people who are infected with HIV have a poor immune response to HHV8, which he says is likely the reason they are at high risk of contracting KS. This type of cancer can be very aggressive in HIV-infected individuals and in organ transplant recipients; a milder, rare form of KS occurs in some older men.

"Our current study shows that healthy adults produce T cells and antibodies that we believe control the first-time HHV8 infection," said Dr. Rinaldo. "The only signs of disease that we see, if any, are transient, flu-like symptoms." Like all herpesviruses, HHV8 remains, but in a latent form, after the initial infection.

In addition, the study demonstrates that HHV8 infection causes no negative changes in a patientís immune system, which is not the case with other, similar herpesviruses such as Epstein-Barr virus, the cause of infectious mononucleosis.

Dr. Rinaldo and his research team screened blood specimens taken over the past 15 years from 108 men participating in the Pitt Menís Study. They found five HIV-negative men who became infected with HHV8 during that period.

A review of these patientsí clinical records showed that around the time of infection they experienced fatigue, enlarged lymph nodes, mild fever, diarrhea and/or mild skin rash. All symptoms were temporary, and the five men had no lingering changes in their health. Moreover, the men had a strong immune response to the virus during the first few years of HHV8 infection that eventually subsided as the virus was controlled. This included formation of killer T cells and antibodies directed against different proteins made by the virus. The flu-like symptoms and anti-HHV8 immune responses were not found in HIV-negative men who did not have primary HHV8 infection and who were examined at the same time by clinicians.

"While our study showed that first-time HHV8 infection is either asymptomatic or associated with several different mild, flu-like symptoms, many more cases of HHV8 infection must be analyzed before we can say definitively what specific clinical syndrome the virus causes in healthy adults," said Dr. Rinaldo.

To follow up on the current study, he and his research team have begun looking at how an HIV-positive patientís impaired immunity can lead to KS, and they are developing ways of boosting immunity to impede that progression. "We hope that this research will eventually lead to a vaccine for prevention of HHV8," he said. This project, too, is part of the Pitt Menís Study. Directed by Dr. Rinaldo, the Pitt Menís Study is the Pittsburgh site of the Multicenter AIDS Cohort Study (MACS), one of the longest-running studies of the natural history of AIDS and associated diseases.












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