WEDNESDAY, Oct. 31, 2001 (HealthDayNews) -- A benign strain of herpes may run molecular interference in a way that shields cells from initial infection by the AIDS virus, new research shows.
Scientists in the United States and Europe say human herpesvirus 6 (HHV-6) gums up the molecular ports HIV-1 uses to enter host cells. However, they add, the harmless microbe may be a little too protective, stimulating HIV to seek other routes to infect its targets and promoting more severe disease.
"You can consider herpesvirus as a double-edged sword," says Leonid Margolis, a researcher at the National Institute of Child Health and Human Development and a co-author of the study. "You can imagine that in the early stages, [HHV-6] would be beneficial to prevent spreading of the [AIDS] virus, and at the later stage, full-blown infection, it may play a deteriorating role."
The findings, which appear in the November issue of Nature Medicine, are the latest in a string of studies suggesting that HIV might be hampered by less deadly organisms that prevent it from getting a foothold in the body.
Earlier this year, for example, researchers reported that patients infected with both HIV and a sleepy form of hepatitis called GB virus type C (GBV-C) are much less likely to die of AIDS in the short term than patients not infected with the second virus.
Another study showed that AIDS patients with scrub typhus, a bacterial infection, tend to do better than those not carrying both microbes.
In the latest work, Margolis and his colleagues in the United States and Italy focused on HHV-6. This strain of herpes is probably present in most people, if not everyone, Margolis says. It's believed to be completely harmless in adults, though it can cause a brief rash in babies.
HIV-1's target of choice are CD4 T cells, immune agents that help rid the body of microbes. To enter CD4s, the virus docks with molecules, called receptors, on their surface.
But HIV prefers different receptors at different phases of infection. Early on, for example, it seeks out receptors called CCR5, while in later, more mature disease, it mysteriously changes tack and opts for a variety known as CXCR4.
Margolis' group saw that when HHV-6 infects bricks of tonsil cells -- which are good representatives of the true lymph system and much more realistic than conventional cell cultures -- they produce a flood of a molecule called RANTES (short for "regulated on activation, normal T cell expressed and secreted"). This chemical acts as receptor glue, sealing up CCR5 receptors in a way that keeps HIV-1 at bay. When the researchers added RANTES to HIV-infected cells in a dish, virus levels dropped.
However, HHV-6 only appears to protect T-cells when they're infected with early-stage variants of HIV. The combination of the herpes virus and later-stage HIV leads to more, not less, killer virus. More mature HIV-1 enters cells through the CXCR4 receptor on CD4s.
Indeed, Margolis says, since HHV-6 is so prevalent, it may play a role in HIV's puzzling change of favorite T-cell receptors. The researchers now hope to study HHV-6 levels in people who have HIV, and they'll also examine other herpes strains to see if they behave similarly.
Drug makers have recently sought to turn RANTES into a therapy not only for AIDS but for other immune-related conditions, such as diabetes.
Dr. Alan M. Krensky, the Stanford University scientist who defined the molecule in 1987, says no company has yet achieved a breakthrough with the substance. But he remains optimistic, particularly because RANTES can both stimulate and suppress immune activity.
"If you have immune cells and would like to get rid of them, you'd like to block RANTES. If you don't have enough immune cells [and] would like to bring them in, then you add RANTES," Krensky says. "There's lots of evidence that it would work" in patients.
Last year, for instance, an National Institutes of Health study found that people with a gene change that increases the activity of the molecule were more prone to HIV infection -- but developed AIDS more slowly -- than those without the variation.
Experts say GBV-C might also be a novel target for therapies to fight AIDS. But they caution that the virus must be better understood -- it was first identified in 1995 -- before it can be exploited as a treatment. About 40 percent of HIV-positive people also carry GBV-C, which does not cause hepatitis or any other known clinical symptoms. The organism is a so-called flavivirus that's related to those that cause yellow and dengue fevers.
Dr. Jack Stapleton, the University of Iowa physician who first linked GBV-C infection and less-aggressive HIV, says, "There's a large clinical observation that having GBV-C is associated with a reasonably good outcome" of AIDS. The same remains to be seen for "co-infection" with HHV-6, he notes.
What To Do
More than 33 million people worldwide are infected with the AIDS virus. To learn more about the biology of HIV, try the University of California at San Francisco.
For more on AIDS, visit the Centers for Disease Control and Prevention or the World Health Organization.
