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Study finds HIV protein can drive immune cells away

Massachusetts General Hospital (MGH) researchers may have provided another clue to the mystery of how HIV, the virus that causes AIDS, evades the defenses of the immune system. In the May issue of the Journal of Virology, a team from the Partners AIDS Research Center at MGH describes finding how a key protein that helps the virus enter its target T helper cells may also keep away the T killer cells that should destroy HIV-infected cells.

One of the big questions in understanding HIV is why we can see immune responses that are effective in the test tube but do not eradicate the virus in the infected patient, says Mark Poznansky, MD, PhD, of the Partners AIDS Research Center (PARC) and the MGH Infectious Disease Unit, the papers senior author. We have identified a potential new mechanism by which pathogens can repel immune cells and thereby evade the immune system.

In 2000, Poznansky and colleagues published a report that found how a protein called SDF-1, known to attract immune cells, can actually repel T cells when present in elevated quantities. SDF-1 is a chemokine, a protein normally produced to summon immune cells to the site of an injury or infection. The molecule is known to interact with a T cell receptor called CXCR4 which also is used by HIV when it binds to and enters T helper cells. Investigating whether HIV infection involves the same kind of cellular repulsion observed in the earlier study a process the researchers dubbed fugetaxis seemed a logical next step.

In a series of experiments led by Diana Brainard, MD, a research fellow in Poznanskys lab, the team first found that while low concentration of gp120, the HIV protein that interacts with CXCR4, attracted T killer cells, higher concentrations induced the immune cells to move away. They then showed that it was the specific interaction of gp120 with CXCR4 that controlled T cell movement, and that the same repulsion could be produced specifically with T killer cells p
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
3-May-2004


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