Study Finds New Approach That Stops HIV at Earliest Stage

by Sreeraman on  February 28, 2008 at 4:13 PM AIDS/HIV News
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It has been explained by some researchers that when the virus enters the body through sexual contact, it steers clear of being interrupted by the dendritic cells of the immune system that stand guard for invaders at the mucosal lining of tissues. However, the virus fools these cells, and attaches to a particular receptor protein, known as DC-SIGN, on the dendritic cells. In this way, HIV manages to evade immune detection while the dendritic cells travel to the ultimate goal of the virus: immune T-Cells in the lymphoid system, which is later infected by HIV, setting up a deadly infection that spreads.

The second discovery is that there’s an antibody that is able to signal immune destruction of the virus. On of the study’s first author, Sheng-Kai Wang, a graduate student in Wong’s laboratory has said that this antibody, 2G12, protects people who have it against HIV progression, but there are very few of those who are infected put up such an immune reaction.

The researchers have defined the details of the action of the antibody and found that it recognizes a dense cluster if sugars on one region of the virus’s spiky protein coating, which is, strikingly, the same area that HIV uses to bind to the DC-SIGN protein on dendritic cells.

Previously, the researchers designed and tested synthetic constructs to mimic the clusters of sugars recognized by 2G12 that could form a vaccine. They invented a process called programmable one-pot synthesis that made it possible for them to quickly assemble many types of carbohydrate structures by placing a large number of chemical building blocks into a reaction vessel to make sequential chemical reactions.

Thus, the Scripps Research team built a dendron structure that can bind to the DC-SIGN protein, preventing HIV from doing so, and which also mimics the sugar clusters that 2G12 binds to, prompting the immune system to produce destructive antibodies to the viral coat.

“The sugar structure is able to inhibit HIV from binding to DC-SIGN on dendritic cells in vitro. But to become a vaccine, as tested in mice, the sugar structure has to be attached to a carrier as the sugar structure alone is too small and too weak to be used as a vaccine. The sugar-carrier conjugate will also inhibit HIV from binding to DC-SIGN," said Wong.

The study is published in a recent issue of the online Early Edition of the Proceedings of the National Academy of Sciences (PNAS).

Source-ANI
SRM/K
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