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Anti-parasite drug may provide new way to attack HIV
Date:1/31/2008

nvader. Macrophages, on the other hand, are designed to roam the body engulfing and digesting dead tissue and bacteria. To assume this special role, they give up the ability to divide.

Unlike most viruses in its family, HIV has the ability to infect both non-dividing macrophages and rapidly dividing T cells, a key to its deadliness. Given its choice, HIV would prefer to infect rapidly dividing T cells, because with each division comes another opportunity for the virus to copy itself using the T cells genetic machinery. On the other hand, T cells sense they are infected and quickly commit suicide, taking out the virus as well. So quickly do T cells self-destruct that the virus would lose its battle with the human immune system if it did not have long-lived macrophages to hide in during the early years of infection, Kim said.

Many cells can choose to die when they sense cancer-causing flaws in their own genes, or when they are being used as a virus factory. Certain biochemical pathways call for cell suicide and others postpone it, with the two forces counterpoised to control lifespan. Cancer and AIDS result in part from problems in these pathways.

Past studies found that HIV-infected macrophages can serve as viral reservoirs because some unknown factor extends their lifespan. In the brain, for example, macrophages secrete toxins produced by the virus they carry, including the transactivator (tat) protein, which causes nearby nerve cells to commit suicide. When enough nerve cells die, patients gradually lose memory, speaking ability and decision-making skills despite the best available treatment. Presumably, such toxicity should cause brain macrophages to self-destruct as well, but that is not the case. Macrophages live on, and no one had known why until the publication of two papers by Kims team, one today and the other in January 2007.

The earlier paper reported that macrophages infected with HIV live abnormally long, and that
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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