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UCLA reserachers discover why AIDS virus targets the gut

iClinic - August 23, 2000


UCLA AIDS Institute researchers have solved a piece of the mystery as to why the AIDS virus targets the gut, explaining why unprotected oral and anal sex with an infected partner holds even greater risk than previously believed, reported this week's issue of AIDS.

"We knew from previous research that HIV prefers to stake out its home base in the gut," said Dr Peter Anton, principal investigator and associate professor of digestive diseases. "Now we understand why."

Anton and his colleagues drew blood samples and gut biopsies from eight HIV-negative volunteers. Next, they isolated the immune system's infection-fighting T-cells from the samples and compared the number of co-receptors on the surface of each cell. Their findings suggest that HIV may have an easier time penetrating and replicating itself through the gut than the circulatory system.

"We were amazed to discover that the gut's T-cells possessed 7 times more co-receptors than the blood's T-cells," Anton said. "Because HIV can only infect T-cells that possess a certain combination of co-receptors, the gut literally unlocks the door to the immune system so HIV can sneak in."

To test their hypothesis, Anton and his team took the same T-cells they'd isolated earlier and exposed them to the AIDS virus in the laboratory. What they saw proved their suspicions correct.

"The virus reproduced only minimally in the blood cells," Anton said. "But HIV infection spread like wildfire in the gut cells."

The human gut also possesses a physiological disadvantage: T-cells in the gut are protected only by a single layer of cells lining the intestines. If that layer tears slightly during anal intercourse, HIV in the semen or blood can penetrate the lining and attack the exposed T-cells.

"When the virus has only a short time to find a likely target in the immune system before it is destroyed," said Anton, "the gut appears to offer greater vulnerability to HIV infection than many other sites in the body."

Anton believes that the gut's susceptibility to infection may transform into a potential advantage for new clinical treatments. If scientists can develop a drug to block the T-cell co-receptors and introduce the drug into a lubricant or spermicide, for example, they may be able to slow the spread of the virus in the individual and prevent transmission to other people.

Anton warned that people shouldn't interpret the study's findings as a sign that unprotected vaginal sex is less risky than unprotected oral and anal sex. Other researchers have discovered similar findings in the cervical and vaginal cells.

Immunologists have long recognised that the gut contains the greatest number of T-cells, making it the largest organ in the immune system and the body's front defense line against HIV. The intestinal lining contains 50 to 70 percent of the immune system compared to only 2 percent in the blood.

Anton worked with co-investigators Michael Poles, PhD, and the late Janis Giorgi, PhD. The National Institutes of Health, Macy's Foundation and a seed grant from the UCLA AIDS Institute funded the project.
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