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 substance
Contact: John Watson
University of California - San Francisco