The research, presented in the July issue of Nature Medicine, eventually might help researchers better understand and exploit potential weaknesses in HIV.
The researchers studied a large group of homosexual men who were enrolled in the Chicago component of the Multicenter AIDS Cohort Study - an ongoing study of the natural and treated history of thousands of men infected with HIV - headed by Dr. Steven Wolinsky. The confidentiality of all individual study participants was preserved and the study itself was conducted in accordance with the highest recognized and accepted ethical standards.
Los Alamos researcher Bette Korber, Elizabeth Trachtenberg of Children's Hospital Oakland Research Institute and colleagues examined the levels of AIDS virus and a type of T-cell in study participants. In healthy people, these "helper T-cells" help mount an immune response to an attacking organism. Since the AIDS virus attacks and destroys helper T-cells in humans - thereby limiting and eventually destroying a patient's ability to stop the virus from replicating - the number of T-cells within an individual person is an indicator of the progression of the disease; the fewer the T-cells, the greater the level of HIV infection. The researchers were able to track the progression of the disease and the viral load within study participants over time.
Korber, Trachtenberg and colleagues compared viral load and rates of progression to proteins contained on the surface of white blood cells of study participants. The proteins, called human leukocyte antigens (HLAs), perform key functions in helping the body fight infection. They enable one type of T-cell that destroys cells infected with virus to recognize those infected cells. Destroying infected cells stops pathogens from multiplying within those infected cells.
HLAs come in several varieties, or types, and exhibit tremendous genetic diversity. Everyone carries different combinations of these proteins. This diversity ensures that no single pathogen can decimate an entire population. Consequently, human populations tend to maximize and increase the frequency of HLA subtypes to provide better immunity against a range of pathogens. Nevertheless, pathogens evolve over time and develop the ability to disguise themselves and hide from HLAs. The study indicates that the AIDS virus has developed mechanisms to evade the most common immune responses prompted by the most common HLA types.
In fact, Korber and her colleagues found that study participants who had the most common HLA protein types tended to succumb to progression to AIDS significantly more quickly than the participants who had more rare HLA protein types. In other words, the study indicates that HIV is able to outwit the most common HLA types that it usually has to confront, and to overwhelm the body's immune system in individuals with common HLAs much more quickly than it can in patients with rare HLA types.
The researchers also were able to correlate the overall viral load of study participants with their combination of particular HLA types. Those patients with the more common proteins tended to get higher overall viral loads more rapidly than their rare-protein counterparts.
The study suggests that HIV adapts to the most frequent HLA proteins in a population, providing a selective advantage for patients with rare HLA proteins.
Korber and her colleagues cannot be absolutely sure that other subtle biological factors contribute to the association between HLA types and HIV progression. Therefore, Korber says, independent studies on other infected populations will be important to verify or refute the results of this study.
Los Alamos National Laboratory is operated by the University of California for the National Nuclear Security Administration (NNSA) of the U.S. Department of Energy and works in partnership with NNSA's Sandia and Lawrence Livermore national laboratories to support NNSA in its mission.
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Journal
Nature Medicine