Clues that viral gene causes a skin cancer.

Investigators seeking to prove that a recently discovered virus often causes cancer in AIDS patients have uncovered what may be a smoking gun.

Kaposi's sarcoma, until recently a rare cancer, afflicts more than 20 percent of gay men with AIDS. Since 1994, when fragments of viral DNA were found in the cancer's characteristic purplish skin lesions, scientists have suspected that a sexually transmitted virus causes the disease (SN: 9/28/96, p. 206).

Although follow-up studies also placed that virus, human herpesvirus 8 (HHV8), at the scene of the crime, nagging doubts about its guilt remained-in part because scientists couldn't find a cancer-causing weapon wielded by the infectious agent.

Now, researchers at Cornell University Medical College in New York have identified an HHV8 gene whose protein can stimulate cellular proliferation. In the Jan. 23 Nature, they suggest that this gene may explain how the virus triggers cancer. "It's not convincing, but it's tantalizing," comments Philip M. Murphy of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.

The viral gene under suspicion encodes a protein that strongly resembles chemokine receptors, a family of proteins normally found on the surface of immune cells. When chemicals called chemokines bind to the receptors, they signal their respective cells to migrate to sites of inflammation.

While the protein encoded by the HHV8 gene can also bind to chemokines, it provokes a different response by cells. When the scientists simulated an HHV8 infection of cells by adding the viral receptor gene to rat kidney cells, the cells multiplied at an abnormally fast rate. The HHV8 protein "turns on the proliferative response," says Marvin C. Gershengorn of Cornell.

Moreover, the viral receptor does not need to interact with chemokines in order to send signals inside a cell, the researchers report. The viral receptor is permanently "turned on," says Gershengorn. Researchers caution that the case against the viral gene remains circumstan- tial. Current tests, such as those to determine whether the gene's protein can induce tumors, may resolve the issue.

Yuan Chang of Columbia University notes that other HHV8 genes have come under suspicion. "It may be very complicated. This gene or three to four genes may be involved," she says.

If the HHV8 chemokine receptor proves to be the key to Kaposi's sarcoma, scientists plan to look for anticancer drugs that interact with the protein.

"What I would like to do is turn that receptor off," says Gershengorn.