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HIV spreads in therapy-resistant cells

MINNEAPOLIS / ST. PAUL--In a finding that uncovers a new obstacle to preventing or eradicating AIDS, researchers at the University of Minnesota and seven other institutions have found that HIV-1, which is usually transmitted by heterosexual contact, infects and replicates in immune cells whose relative inactivity puts them beyond the reach of current therapies. The study will be published in the Nov. 12 issue of Science.

Previously, scientists thought that HIV could not reproduce itself inside T cells, the major targets of the virus, unless the cells had been activated, said Ashley Haase, Regents Professor of Microbiology at the University of Minnesota and corresponding author of the study. Activation occurs when a T cell encounters a molecule, usually a protein or protein fragment, that signals potential danger and starts the cell on a course that leads to rapid cell reproduction. If the T cell is infected with HIV, the virus takes advantage of the activity by commandeering the cell's reproductive machinery and churning out many copies of the virus, which can then infect other T cells. This cellular piracy kills the T cells.

On the other hand, said Haase, T cells that have not been activated ("resting" T cells) were thought to provide little or no opportunity for the virus to replicate and spread. The theory was that the virus first infected other white blood cells known as macrophages and dendritic cells, and these later passed the infection to activated T cells. But studies spearheaded by Zhi-Qiang Zhang, a research associate in Haase's department, showed otherwise. In monkeys infected with SIV (the simian form of the virus), viral particles were detectable mainly in T cells as early as three days after infection--the earliest it was found in macrophages and dendritic cells. Thus, said Haase, the study provides no support for the idea that macrophages and dendritic cells are infected first.

Also at three days post-infection, SIV was found in both
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Contact: Deane Morrison, University of Minnesota
612-624-2346
Beth Israel Deaconess Medical Center
10-Nov-1999


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