San Francisco Chronicle; Thursday, April 2, 1998
David Perlman, Chronicle Science Editor

Known in the world of AIDS as KS, the tumors of Kaposi's once were one of the most widespread infections of the epidemic, and even today at least 25,000 people living with AIDS nationwide suffer from the lesions. But KS may now be finally yielding on two fronts:

-- The sexually transmitted virus that causes the KS lesions has just been firmly identified by a team at the University of California at San Francisco.

-- An international research group has just found that a mysterious protein linked to a hormone produced by pregnant women possesses a remarkable ability to shrink the tumors and build the body's blood supply.

Interestingly, their tests also show that the protein appears to lower blood levels of HIV, the virus that causes AIDS.

Scientists at UCSF are reporting today that they have identified a unique strain of herpes virus as the primary cause of Kaposi's sarcoma, while the international team, led by Dr. Robert Gallo at his Institute of Human Virology in Baltimore, announced yesterday that they have tested their protein and discovered its remarkable range of effects.

A report from the UCSF group published in the New England Journal of Medicine today identifies a herpes virus called HHV-8 as the cause of Kaposi's sarcoma, and the data show that the virus is most often transmitted during homosexual intercourse between men.

The researchers, headed by UCSF microbiologist Dr. Dean Kedes, studied the sexual histories and blood samples of 800 men from San Francisco's Castro neighborhood whose frozen blood had been stored at the San Francisco City Clinic for more than 10 years. Half the men were infected with HIV, the AIDS virus, and half were not.

The researchers detected evidence of the HHV-8 virus in more than 37 percent of the men who reported any homosexual activity within the previous five years but found no virus at all in the exclusively heterosexual men who were part of the study.

Men infected with HIV and also with HHV-8 had a 50 percent chance of developing KS within 10 years, the researchers found. And transmission of the herpes virus increased with the number of years of regular homosexual intercourse, the number of sexual partners the men reported and their history of other sexually transmitted diseases, according to the researchers.

"The major mode of transmission is sexual," said Kedes, and he added: "If you are infected and HIV positive, you're in trouble.'

According to Dr. Jeffrey Martin, an epidemiologist and a co-author of the study, discovering the viral cause of KS can help AIDS specialists understand its specific transmission routes -- whether the virus moves most effectively through oral-genital contact, receptive anal intercourse or oral- anal contact, for example.

PREVENTION STRATEGIES

That knowledge, in turn, can prove invaluable for developing new prevention strategies that would focus specifically on minimizing transmission of the virus by avoiding the most dangerous sexual activities, Martin said. According to Dr. Donald E. Ganem, another co-author of the study, the HHV-8 virus is an essential cause of KS, but the disorder also requires a co-factor such as HIV.

But now that the crucial role of the KS virus is known, Ganem said, drug developers who are continually producing new compounds against other herpes viruses should quickly find and test new drugs against the KS virus.

"This is a truly exciting development," Ganem said, "considering that the virus was only identified in 1994, and now we not only know that it is the cause of KS, but we're also ready to think about new anti-viral drugs and clinical trials to prevent or delay its onset."

The international team that has pinpointed the protein with such powerful effects on both KS and the AIDS virus itself reported its work in the journal Nature Medicine this week and included researchers from Gallo's laboratory as well as from Columbia University, the University of Southern California, and universities in Quebec and Brussels.

FOLLOWING A HUNCH

Although KS itself is not a true cancer, it is called by researchers a "viral sarcoma," and although it is essentially benign, its lesions can and often do become fiercely malignant. Nearly four years ago, scientists who were then investigating KS with Gallo at the National Cancer Institute noticed that pregnant laboratory mice infected with HIV did not develop KS lesions, while HIV-positive males in the same cages did. That led the researchers to a hunch -- and as so often happens in science, the researchers pursued their hunch: The apparent resistance to KS, they reasoned, might be due to a hormone associated with pregnancy.

Found in the urine of women, that hormone of early pregnancy is called HCG, or human chronionic gonadotrophin, and its primary function is to protect the course of the pregnancy so the fetus can develop normally.

Ever since the researchers' hunch, in experiments using laboratory cell cultures as well as mice, monkeys and humans, the international research team has tested the effects of HCG on KS, with curious results.

As they tested crude extracts of the hormone on groups of volunteers with KS, Gallo's colleagues found it had startling results: Something apparently associated with the HCG hormone shrunk some of the KS tumors and unexpectedly lowered the levels of the AIDS virus itself in the bloodstream of some patients dramatically, even though the patients were undergoing no other AIDS therapy.

And equally unanticipated, Gallo reported, the hormone stimulated the bone marrow of some KS patients to increase production of the "progenitor" cells that give rise to the body's supply of healthy red and white blood cells.

As the experiments continued, the scientists found that the crude hormone itself was not the agent, but rather must be one of many protein fragments found in the urine of the pregnant women and linked in some unknown way to HCG.

NEEDLE IN A HAYSTACK

As Gallo described it in an interview this week: "At first, the observation was startling, but as we hunted for the material in urine that seemed to show such effects, we found that more and more proteins were spilling out, and that we needed to look for a needle while were were testing the whole haystack."

By now, the team has found the protein that appears to be the long- sought version of its needle but has yet to determine its chemical structure completely. It remains an unidentified protein that the group has labeled HAF, for HCG- associated factor, and which Gallo predicts will be precisely determined in the next few months.

Whatever that factor proves to be, Gallo said this week, the protein could "open the way for a whole new field of anti-viral research," and a possible pathway to new therapies for KS.

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