19 May 2008

Follicular dendritic cells hide HIV from drugs

Scientists at the Universities of Yang and Johns Hopkins, working under the leadership of Professor Greg Burton, have confirmed the long-standing hypothesis that follicular dendritic cells are a reservoir in which HIV particles remain during treatment, without losing their infectivity.

One of the main problems of HIV treatment/AIDS is the identification of reservoirs of the virus and the development of strategies to eliminate them. The two main reservoirs of HIV, macrophages and latently infected T-lymphocytes, have long been known to specialists, now follicular dendritic cells have been added to this list.

These cells act as a "storage" of the material needed to maintain a humoral immune response. If the level of certain antibodies in the body drops, follicular dendritic cells release proteins that trigger an immune response and increase the levels of specific antibodies.

The mechanisms of follicular dendritic cells work so well that HIV particles remain out of reach of drugs entering the bloodstream, which contributes to the chronization of infection. Until now, scientists have not been able to prove the role of these cells in the persistence of HIV infection.

Follicular dendritic cells are very small and have long processes that firmly root them in the tissue, so attempts to isolate these cells usually end in their destruction.

The authors managed to solve this problem by gentle enzymatic treatment of tissue, isolation of follicular cells using a flow cytometer and antibodies specific to their surface. As experts suspected, the surface of the cells contained bound HIV particles.

The genetic profile of HIV changes as it multiplies in the body. The study of blood samples of treated and untreated HIV-infected patients showed that the untreated virus mutates more often than the treated one, whose replication is suppressed by the action of drugs.

Using supercomputers, the authors recreated the "family tree" of viruses of three patients undergoing treatment at Johns Hopkins University. Blood samples of patients obtained at different times served as control points for determining the time of capture of viral particles by follicular dendritic cells.

It turned out that dendritic cells bind viral particles throughout the entire period that has passed after infection and maintain a viable infectious population with very high genetic variability, which significantly complicates the treatment of the disease.

Currently, the authors are trying to get a grant to develop strategies for influencing the new reservoir of HIV particles they have discovered.

Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily


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