"SILENT" RESERVOIR OF CELLS INFECTED WITH HIV IS SMALL

May 8, 1997
Media Contact: Marc Kusinitz
Phone: (410)955-8665
E-mail:mkusinit@welchlink.welch.jhu.edu

Like the ancient Trojan horse hiding a silent enemy, some immune system cells in HIV-positive persons carry the genetic information for making HIV and can potentially restart a full-blown infection in patients in whom treatment has reduced AIDS virus to undetectable levels in the blood, according to researchers at Johns Hopkins.

Presumably, this would become a serious concern among patients who are considered treatment successes and taken off drug therapies, the researchers say.

"These HIV genes are a silent, or latent, form of infection that can become active when the immune system responds to ordinary infections by other microbes," says Robert Siliciano, M.D., Ph.D., associate professor of medicine.

Suspected by researchers but only now finally demonstrated, this tiny population of immune system cells holds genes able to make copies of HIV. This suggests that even the best anti-AIDS virus drugs may not be able to ensure a permanent cure for the disease unless these cells are eliminated, Siliciano says.

"These are the cells we're really worried about, these long-term reservoirs of the AIDS virus in the body," says Siliciano, senior author of a report on these findings published in the May 8 issue of Nature. "The good news is that there are many, many fewer of them than we thought. The smaller the reservoir of infected cells, the sooner they will all disappear."

Until now, estimates of how many silent cells existed ranged from 25 percent to one-thousandth of 1 percent, according to Siliciano. In the current study, a team measured how many cells had HIV genes within their chromosomes, showing for the first time, he said, that less than one-hundredth of 1 percent act as Trojan horses. Although most infected T cells die off normally within a few days, some, called memory cells, last for years, posing a long-term threat to patients being treated for AIDS, says Siliciano.

Memory cells are T cells that are generated during the immune system's first attack on a particular microbe. Normally, they then shrink in size and become inactive, "resting" cells, forever on the alert for that microbe and able to leap into action quickly when that microbe re-invades the body. Memory cells also form when a person is vaccinated against the microbe. However, when T memory cells that have latent HIV infection encounter their target microbes and activate, the silent HIV genes make new viruses.

"The viruses released by these T cells infect other T cells and spread the infection again," says Tae-Wook Chun, Ph.D., first author of the paper. Chun was formerly at Johns Hopkins and is now at the National Institutes of Health. "So even if there is no detectable AIDS virus free in the blood or lymph nodes, the infection can flare again if a latently infected T cell specific for any microbe gets activated," says Chun. "And we don't know when these infected T memory cells die or how long they can wait around before they get activated."

Siliciano says because normal memory cells can last years, the latently infected cells may keep an AIDS patient infected for a long time, even if treatment has reduced the number of infected cells to a few.

Other authors of the study include Lucy Carruth, Diana Finzi, Xuefei Shen, Joseph A. DiGiuseppe, Harry Taylor, Monika Hermankova, Karen Chadwick, Joseph Margolick, Thomas Quinn (also of National Institutes of Health), Yen-Hong Kuo, Ronald Brookmeyer, Martha A. Zeiger and Patricia Barditch-Crovo.


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