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How HIV disables the cells' call for help

The HIV virus hides out in the very immune system cells that are meant to protect the body from viral infection. But how does it prevent these cells from mounting a full-scale attack against the invader? In research published today in the Journal of Clinical Investigation, a team at the Weizmann Institute of Science has shown how a part of a protein on the virus' outer surface interferes with the cells' normal immune response. But their work may have wider implications: this molecular fragment, which has such a devastating effect in one disease, might turn out to be an effective treatment for other disorders such as rheumatoid arthritis.

In the initial stages of HIV infection, the protein coatings of the viruses fuse with the outer membranes of T cells ?immune system cells that recognize foreign invaders and alert other types of immune cell to come to the rescue. The genetic material of the virus, which is basically a strand of RNA, then forces the cell's DNA to make copies of it. Newly minted viruses created by the host DNA later break out of the cell membrane to infect other cells. Many believed that the very act of breaking into T cells and hijacking their DNA was enough to destroy the ability of these cells to call up immune support.

But Institute scientists Prof. Yechiel Shai of the Biological Chemistry Department, Prof. Irun Cohen of the Immunology Department and graduate students Francisco Quintana and Doron Gerber thought there must be more to the story. T cells identify invaders using receptors, like security antennae, on their outer walls. A virus, especially one with its own surface equipment for seeking out specific T cells, would be hard-pressed to slip past these receptors without raising the alarm. The scientists surmised that the virus must be able to actively disable some part of the immune cell's system.

They investigated a peptide fragment called FP (fusion peptide), a segment of the HIV protein gp41 found on the viral envel
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Source:American Committee for the Weizmann Institute of Science


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