Critical Kaposi's growth factor identified.

Critical Kaposi's growth factor identified

A new study from the laboratory of AIDS-virus codiscoverer Robert C. Gallo adds an intriguing clue to the medical mystery of Kaposi's sarcoma. The work provides a valuable focus for researchers attempting to develop drugs against this cancer-like proliferation of blood vessels and skin cells, which has become a hallmark of AIDS.

Once associated primarily with elderly Jewish or Mediterranean men and with people on immune-suppressing drugs, Kaposi's sarcoma mushroomed into a U.S. epidemic as the AIDS virus (HIV) became prevalent. Today, it is at least 20,000 times more common in people with AIDS than in the general U.S. population and 300 times more prevalent in AIDS patients than in other immunosuppressed groups. Despite years of intensive investigation, researchers have yet to identify what triggers the sarcoma.

In 1988, Gallo and his co-workers reported they had discovered a way to grow Kaposi's cells in culture, allowing researchers to study the cells' growth requirements (SN: 10/29/88, p.283). Their preliminary work showed that the cells grew only in the presence of an unidentified growth factor released from HIV-infected white blood cells. Now, in the May 3 NATURE, they report the identity of that critical factor.

The culprit appears to be a viral protein called tat. Produced by HIV-infected white cells, tat empowers the virus to complete its replication cycle inside those cells. The new research, led by Barbara Ensoli of the National Cancer Institute in Bethesda, Md., is the first to show that tat can escape from HIV-infected cells and that a viral regulatory protein can directly stimulate the growth of Kaposi's cells, Gallo told SCIENCE NEWS.

Although the culture studies suggest tat is critical to either the genesis or the progression of Kaposi's sarcoma in HIV-infected people, the finding may also prove compatible with a somewhat radical hypothesis suggested earlier this year (SN: 2/3/90, p.78). In the Jan. 20 LANCET, researchers at the Centers for Disease Control in Atlanta proposed that at least some cases of Kaposi's may result from an as-yet-unidentified, sexually transmitted agent. They based their suggestion on epidemiologic evidence that Kaposi's sarcoma is much more prevalent in patients who got AIDS sexually than in those who got AIDS from intravenous drug use or from contaminated blood products. This hints that Kaposi's sarcoma may arise from a sexually transmitted agent that is frequently passed along with HIV but doesn't survive well when passed intravenously.

Also in the Jan. 20 LANCET, scientists at the New York University Medical Center described case histories of six homosexual or bisexual young men who had Kaposi's sarcoma despite negative HIV tests, again supporting the possibility of an independent, sexually transmitted causative agent. Taking into account similar reports by other researchers, the team hypothesized that a Kaposi's-causing organism may have become widespread among homosexual men at about the same time as the HIV epidemic took hold.

It remains to be seen whether a mystery organism indeed triggers Kaposi's sarcoma -- with or without HIV's help -- and whether that organism codes for the production of a tat-like protein. In the National Cancer Institute experiments, only tat-producing cells supported Kaposi's sarcoma growth in culture, and anti-tat antibodies (which bind up available tat in the culture medium) blocked it. Still, Gallo says, "whether tat is enough in vivo, we don't know."

In any case, he concludes, the latest findings provide additional incentive to develop drugs that block tat's activity--a goal already high on AIDS researchers' priority list, since tat is critical to HIV replication.