( Scientists have discovered the mechanis...) Gladstone investigators discover how resting T cells avoid HIV infection

Scientists have discovered the mechanism that enables some CD4 T cells -- the main target of HIV -- to thwart the virus. The discovery, reported on April 13 in the online version of Nature, could open the door to an entirely new strategy for preventing the spread of HIV infection in the body's cells, according to the senior author of the study, Gladstone Institute of Virology and Immunology Director Warner C. Greene, MD, PhD.

The researchers, led by Ya-Lin Chiu, PhD, a postdoctoral fellow in the Greene lab, investigated why resting, nondividing CD4 T cells are impervious to HIV infection, while activated, dividing CD4 T cells are not. The team discovered that a potent antiviral factor called APOBEC3G (A3G) is the key.

The team, working in cell culture, found that A3G exists in two different-sized forms -- a small form that actively repels the virus, and a large form that is completely ineffective against it. Moreover, they detected only the small form in resting CD4 T cells, where HIV fails to grow, and only the large form in activated CD4 T cells, where the virus efficiently grows and wreaks havoc. They further showed that blocking production of the small, active form of A3G in resting CD4 T cells was sufficient to make these normally resistant resting cells highly susceptible to HIV infection.

"Until now, the prevailing belief has been that HIV failed to infect resting T-cells due to a simple lack of some essential factor or nutrient," says Greene, a professor of medicine, microbiology and immunology at the University of California, San Francisco. "This study now shifts the paradigm, showing that resting CD4 T cells actively repel HIV infection through the action of the small, enzymatically active form of A3G, which stops the virus in its tracks."

CD4 T cells are a class of lymphocytes, or white blood cells, that fight infection by orchestrating immune responses. They have the ability to recognize specific antigens -- foreign substan
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Source:UC San Francisco

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