Discovery of proteins necessary for HIV release suggests possible new therapeutic targets

Dr. Wesley Sundquist, professor of biochemistry at the University of Utah, will present at the Experimental Biology 2003 meeting in San Diego on his work in elucidating how HIV is manufactured and assembled in the cell.

The raison d’être of a virus such as HIV, if a non-living thing can be said to have one, is to turn a host cell into a factory that churns out virus copies and releases them to infect other cells. Dr. Sundquist’s research has focused on discovering the mechanisms underlying this manufacturing process.

By identifying and characterizing the structures of specific cellular proteins that are crucial to assembling HIV, Dr. Sundquist is providing potential new targets for future anti-HIV drugs. For example, he and his colleagues were the first to show that a protein called TSG101 is required for HIV release. HIV needs TSG101 in order to escape from its host cell in a process termed budding. Dr. Sundquist’s team has also determined the structure of the part of TSG101 to which HIV binds. Finding ways to alter this structure or otherwise block its binding to HIV theoretically would prevent budding and slow or halt the infection.

Sundquist is the 2003 recipient of the ASBMB-Amgen Award. Among the research strengths for which Dr. Sundquist has been lauded is his use of a wide palette of experimental techniques to determine the structures of key components in HIV assembly. By incorporating nuclear magnetic resonance imaging, cryogenic electron microscopy, genetic analysis, and other technologies into his lab, he has produced compelling findings that have made him a leader in the field of HIV research and structural biology.

Perhaps more significantly, Dr. Sundquist not only produces vivid descriptions of important molecular structures but also uses his findings to predict the potential effects of manipulating these molecules. Having identified the three-dimensional structures of two proteins, named Matrix and Capsid, which are key components of the HIV assembly line, Dr. Sundquist and his colleagues now aim to understand exactly how these proteins help assemble the virus. Their studies will guide the development of drugs that target those proteins.