Weijing He, M.D. (pictured), senior post-doctoral fellow in the laboratory of Sunil K. Ahuja, M.D., is first author of the Cell Host & Microbe paper. Dr. He has been a vital part of research establishing the concept of HIV ‘genetic risk groups.’
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Contact: Will Sansom, (210) 567-2579

SAN ANTONIO (July 31, 2008) — An HIV-AIDS discovery by UT Health Science Center San Antonio researchers and their collaborators made the front page of The New York Times in July and ran in media outlets throughout the world.

The journal Cell Host & Microbe announced the finding July 16. The research team reported that while a genetic variation may have protected people of African descent against a pandemic of malaria long ago, it now appears to increase their susceptibility to HIV infection.

The variation is one of the first genetic risk factors for HIV to be identified only in those of African descent, and puts a spotlight on the differences in our genetic makeup that play a critical role in susceptibility to HIV-AIDS, the researchers said.

Hemant R. Kulkarni, M.D., assistant professor of medicine in the Division of Infectious Diseases and a member of the Veterans Administration Research Center for AIDS and HIV-1 Infection, is a co-author of the new report and several other papers on HIV-AIDS genetic susceptibility.

Researchers study gene expressing Duffy antigen
In a population of 1,266 HIV-positive U.S. military personnel and 2,000 non-infected healthy personnel, researchers studied the gene that expresses Duffy antigen receptor. (The antigen was named for an early hemophiliac patient named Duffy.) This molecule on the surface of red blood cells serves as the docking site for the malaria species Plasmodium vivax.

Genetic variation may boost susceptibility to HIV
“Subjects who have a genetic variation do not express the Duffy antigen receptor and are known to be less likely to contract malaria vivax,” said Sunil K. Ahuja, M.D., professor of medicine, microbiology, immunology and biochemistry at the Health Science Center and a senior lead author of the study. “But now it turns out having this variation is a double-edged sword.”

“Duffy antigen influences levels of inflammatory and anti-HIV blood factors called chemokines,” noted Weijing He, M.D., senior post-doctoral fellow in Dr. Ahuja’s laboratory and first author of the paper. “Other as-yet undefined host factors likely exert population-specific effects on HIV-AIDS, such that individuals of European or African descent are likely to have distinct host factors that affect their respective susceptibilities to HIV and AIDS.”

Gene variation may explain why more people in sub-Saharan Africa have HIV
HIV affects 25 million people in sub-Saharan Africa today, an HIV burden greater than any other region of the world. Sexual behavior and other social factors do not fully explain the large discrepancy in HIV prevalence compared to other populations worldwide, the authors note.

“In sub-Saharan Africa, the vast majority of people do not express Duffy on their red blood cells,” said senior lead author Robin A. Weiss, Ph.D., of University College London. “This is one of the first genetic factors particularly common in Africans that has been shown to confer more susceptibility to HIV.”

Paradoxically, the research team noted that once people become infected, the Duffy-deficient variation actually prolongs survival. Again, this was noted in the U.S. military personnel population.

Long-term data support study findings
“This is a clinical cohort of people who have been followed for nearly 25 years,” said a senior lead author, Matthew J. Dolan, M.D., of the Infectious Disease Clinical Research Program at Uniformed Services University in Bethesda, Md. “The advantage is we have long-term follow-up, the population is ethnically balanced between European and African Americans, and everyone has had the same employer, health care and HIV medication access.”

Drs. Ahuja, He and Dolan; Hemant Kulkarni, M.D.; and other co-authors have published a series of papers on other genetic variations that play a role in HIV-AIDS susceptibility. “The Duffy finding is another valuable piece in the puzzle of HIV-AIDS genetics,” Dr. Ahuja said.

Dr. Ahuja is director of the Veterans Administration Research Center for AIDS and HIV-1 Infection in the South Texas Veterans Health Care System. Drs. He and Kulkarni are members of the HIV/AIDS Center.

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The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $576 million, the Health Science Center is the chief catalyst for the $15.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $35 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 23,000 graduates (physicians, dentists, nurses, scientists and allied health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, allied health, dentistry and many other fields. For more information, visit www.uthscsa.edu.