Scientists discover proteins involved in spread of HIV-1 infection

Bethesda, MD - An international team of researchers has identified a family of proteins that are involved in HIV-1 budding from host cells, and are therefore likely to be essential for the spread of the virus. Targeting these proteins and the proteins they interact with could lead to potential new therapies for HIV-1 as well as other viruses that use the same budding mechanism.

The research appears as the "Paper of the Week" in the August 20 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Like other enveloped viruses, HIV-1 needs to bud from host cells in order to spread infection to other cells. To do this, the virus hijacks a pathway that normally sorts proteins into cellular compartments called multivesicular bodies (MVB) for destruction by lysosomes. The HIV Gag protein contains a specific sequence of amino acids which it uses to recruit the human tumor susceptibility gene 101 (TSG101). The virus then uses TSG101 to take control of the protein sorting and vesicle formation machinery and use it for its own purposes.

Previously, scientists determined that the yeast version of TSG101, called Vps23p, binds to two other proteins, Vps28p and Vps37p, to form the Endosomal Sorting Complex Required for Transport (ESCRT-I) which then participates in the protein sorting and packaging process.

However, the analogous pathway in humans is not quite as defined--scientists have found the human equivalent of Vps28p, but not Vps37p. Missing this protein has made it hard to understand what exactly goes on in humans.

Now, Wesley Sundquist, professor of biochemistry at the University of Utah, and his colleagues report that they have found the human version of Vps37p. "Our paper describes the identification of the human VPS37 proteins. This is a necessary step both for understanding how HIV-1 buds from cells and for defining the

Contact: Nicole Kresge
American Society for Biochemistry and Molecular Biology

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