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T Cell Housekeepers May Spread HIV

A group of proteins that generally function to keep certain immune system cells neat and tidy may also facilitate dirty transactions. In a report published today in the Proceedings of the National Academy of Sciences, researchers linked this group of proteins, dubbed the ubiquitin-proteasome system, to the spread of HIV from one cell to another.

Ulrich Schubert of the National Institute of Allergy and Infectious Diseases (NIAID) and his colleagues decided to see what would happen if they chemically blocked the system in so-called CD4+ T cells infected with HIV. Intriguingly, the block significantly hampered the virus' ability to exit and spread to new cells. Under normal circumstances, virus particles exit the T cell by way of budding: snatching a swatch of the cell's membrane, the virus wraps itself up in an envelope that can fuse with the membrane of a neighboring cell, enabling easy access to the new host. But when the proteasome was blocked, a number of the budding particles fumbled with their pilfered membrane cloaks, failing to yank themselves free. What's more, those viruses that did succeed in breaking free were unlikely to mature properly, thereby diminishing their ability to infect.

"This discovery provides another example of how HIV manipulates T cells for its own survival," NIAID director Anthony S. Fauci observes, "and sheds light on a poorly understood type of virus-cell interaction." But an anti-HIV drug based on blocking the proteasome is unlikely, according to Schubert's NIAID colleague, Jonathan Yewdell. "The proteasome is important for almost all cellular functions, so such drugs would be toxic to the cell," he notes. Still, the researchers agree that further investigations into the interactions between HIV and the ubiquitin-proteasome may lead to new ways to tackle the virus.

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