( ces such as toxins bacteria or enviro...) Gladstone investigators discover how resting T cells avoid HIV infection

ces, such as toxins, bacteria or environmental factors -- through receptors on their surfaces. Roughly 95 percent of CD4 T cells in the blood stream exist in a resting, inactive state, awaiting the appearance of their specific antigen. When they detect its presence, they spring into action -- growing and dividing, releasing cytokines (proteins that the immune system uses to communicate between cells) and recruiting and activating additional T cells. The new study shows that this activation process dismantles the highly effective A3G antiviral shield, making these cells highly susceptible to HIV infection.

Greene's group is now looking at ways to use this new knowledge therapeutically. One approach would involve converting the ineffective, large form of A3G into the protective, small form in activated CD4 T-cells. In this case, the goal would be to identify small molecules that promote the disassembly of the large A3G complex, which is shown by the Gladstone team to contain not only A3G but also a cellular RNA and possibly other host proteins.

A parallel strategy would involve finding ways to prevent the small form of A3G from converting to the large form in the first place, during the process of T cell activation. However, notes Greene, scientists would first need to determine whether preserving the antiviral shield provided by small A3G in activated and dividing CD4 T-cells does not produce any deleterious effects. These could include the early death of these cells or the creation of mutations in the chromosomes that might lead to cancer.

"The possibility of exploiting the natural and potent antiviral properties of A3G to control HIV infection is very exciting," says Greene. "We have learned a great deal from our studies of how the resting CD4 T cell resists HIV. Now, the challenge is for scientists at the Gladstone Institute of Virology and Immunology and elsewhere to translate these basic discoveries into novel treatments that could benefi
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Source:UC San Francisco

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