B R E A K T H R O U G H S
Identifying genetic mutations linked to HIV/AIDS
These questions have been answered by a husband-wife team at the Health Science Center, Sunil K. Ahuja, MD, assistant professor in the departments of medicine and microbiology, and Seema S. Ahuja, MD, assistant professor in the department of medicine, in collaboration with Lt. Col. M. J. Dolan of Wilford Hall Medical Center. The research team discovered gene mutations associated with altered rates of HIV-1 disease progression in African Americans--and possibly also in Hispanics--but not in Caucasians. In their findings, published in the July issue of Nature Medicine, they also describe a mutation associated with an accelerated HIV disease course.
The researchers examined mutations in genes for immune molecules called chemokines and chemokine receptors in 1,090 subjects infected with HIV-1, which invades certain immune cells by taking advantage of molecules on the surface of those cells. One group of molecules used by HIV to enter cells is called chemokine receptors. When two or more receptors are used in tandem, they are referred to as co-receptors.
"The first co-receptor that HIV latches onto is the CC chemokine receptor 5 (CCR5)," said Dr. Sunil Ahuja, an infectious diseases expert. "When the virus begins to mutate, it loses its affinity for CCR5 and attaches itself to other co-receptors, such as CC chemokine receptor 2 (CCR2), to enter other immune cells of the body, such as T cells."
Individuals who have a genetic mutation that completely prevents expression of CCR5 resist acquiring HIV, according to Dr. Ahuja. He also described another mutation in a different gene for a chemokine called SDF that actually accelerates the progression of HIV toward AIDS. People with this particular mutation die about three years more quickly on average than those who lack the mutation.
In addition, the researchers identified a new mutation in the CCR5 genes that is associated with a delay in disease progression. This mutation is situated in a region of the gene that controls the amount of CCR5 produced by the cell.
Dr. Ahuja stated he would not advocate genetic testing for patients at high risk for acquiring HIV or for those already infected with the disease. "These are association studies, not cause-and-effect studies," said Dr. Ahuja. "We still are not certain how these mutations exert their protective effects, nor do we know for sure why the same mutation present in African Americans and Caucasians is only beneficial in the former group."
The Ahuja-Dolan team receives funding from the Kleberg Foundation, the Department of Veterans Affairs, the National Institutes of Health and other local grants.
