Immune factor inhibits the spread of HIV.

After infection with HIV, the AIDS-causing virus, people usually experience a period of good health before a devastating decline of immune function results in a host of opportunistic infections. Some people, however, remain asymptomatic for a remarkably long time (SN: 3/18/95, p.172).

Researchers are just now beginning to determine which aspects of the immune system keep HIV at bay. A team of San Francisco researchers has pinpointed a substance secreted by certain immune cells that prevents the virus from replicating. The finding could lead to new strategies for controlling HIV infection.

The substance, known as cell antiviral factor (CAF), suppresses the virus' ability to spread from cell to cell through the immune system. "Understanding how CAF inhibits the virus could give us insights into new therapies for HIV," says immunologist Jay A. Levy of the University of California at San Francisco.

Levy's group identified CAF in the mid-1980s while trying to grow HIV. The researchers found they could isolate large amounts of the virus from white blood cells, or T cells, of late-stage AIDS patients, but not from the blood of newly infected or asymptomatic patients.

To identify what was inhibiting HIV production in asymptomatic patients, the team separated the T cells into CD4 cells, which help trigger immune responses and which form the target of HIV infection, and CD8 cells, which destroy infected cells. Populations of HIV-infected CD4 cells produced large amounts of HIV, whether they came from asymptomatic or late-stage AIDS patients, but adding CD8 cells from long-term survivors or uninfected people shut down HIV production. CD8 cells of late-stage AIDS patients had no effect.

Further studies indicated that the CD8 cells showing antiviral activity secreted the substance researchers named CAF. Researchers also found that CD8 cells from long-term survivors of HIV infection maintain the ability to stymie the virus. Still, no one knew at what stage CAF shuts down HIV.

New information presented by Levy's colleague Carl E. Mackewicz at the Ninth International Congress of Immunology in San Francisco now indicates that CAF inhibits HIV replication within CD4 cells at an early stage, preventing the virus from making copies of itself. However, CAF doesn't disrupt the normal functioning of infected CD4 cells. Because the cells continue to perform immune functions while CAF suppresses the virus, Levy sees hope for a therapeutic strategy against HIV.

Mackewicz and Levy both point out that they still don't know what CAF is. "The factor is produced in such small amounts that isolating it has been and will be extremely difficult," says Mackewicz.

Immunologist Alan L. Landay of Rush-Presbyterian--St. Luke's Medical Center in Chicago agrees that therapeutic uses for CAF hinge upon knowing its molecular makeup, but he notes that the San Francisco team's elucidation of the way CAF inhibits HIV replication will help in developing new ways to fight HIV.