The Combination Punch

By Christine Gorman

Of the many afflictions that descend upon AIDS patients, cancer is one of the most relentless. Doctors have long believed that various forms of malignancy arise indirectly because the AIDS virus, HIV, damages the immune system, making the body vulnerable to cancer-causing agents, whatever they may be. But that assumption could be wrong, at least in some cases. New evidence suggests % that HIV itself can be the trigger for cancer, directly causing cells to turn malignant.

This news comes from the University of California at San Francisco, where researchers studied AIDS patients with lymphoma, a cancer in which lymph cells grow wildly. The scientists found that HIV had invaded the cells and, in some instances, activated cancer-causing genes that are normally dormant.

If the findings, which are reported in the journal Cancer Research, are confirmed, they may mean that a variety of viruses of the same type as HIV, called retroviruses, could also cause cancer. Moreover, the results raise concerns about two major areas of research: the efforts to develop an AIDS vaccine and to cure other diseases through so-called gene therapy. Attempts to vaccinate people by using a weakened strain of HIV may turn out to be dangerous: the inoculation might offer protection against AIDS but cause a cancer. Doctors now experimenting with gene therapy use retroviruses as molecular taxis to transport bits of fresh genetic material into cells in an attempt to replace defective genes. Gene therapists say the retroviruses have been altered so that they cannot reproduce. Yet the scientists acknowledge a small risk that the viruses could cause cancer.

In the San Francisco study, Dr. Michael McGrath and Dr. Bruce Shiramizu examined tissue from more than two dozen AIDS patients who suffered from lymphoma. In the majority of cases, they found what any AIDS researcher would expect. After infecting the lymph system, HIV uses its genetic material, RNA, as a template to produce viral DNA, which randomly incorporates itself into the cell's DNA. But in a few cases, the viral strands zeroed in on a particular stretch of cell DNA. When the investigators looked more closely, they discovered what is known as an oncogene nearby. Responsible for normal growth during development, oncogenes are supposed to lie low in adulthood. However, they can trigger cancer if they remain stuck in the on position later in life.

Like detectives who determine how a fire broke out by studying the way in which the house burned down, the researchers surmised that HIV had somehow switched on the dormant oncogene, causing the cell to divide repeatedly. "It surprised us at first," McGrath recalls. "We thought it was coincidence, but then it happened three more times and we knew we were on to something." The new cancer cells released yet more virus, which activated oncogenes in other cells, starting a deadly chain reaction.

The research suggests a possible strategy for treating lymphoma in these patients: attack HIV with antiviral drugs like interferon. "We don't know whether turning off HIV will turn off the cancer gene as well," McGrath admits. "But it's an approach we are eager to pursue."

With reporting by Dick Thompson/Washington