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A University of Utah biochemist has been awarded a $19.2 million National Institutes of Health grant to establish an HIV research center and study the molecular biology of the AIDS-causing virus.
Principal investigator Wesley Sundquist and a team of 11 researchers, including five from the U., will attempt to better understand how HIV hijacks "host" cells, forms new virus particles and spreads to other cells.
"We're looking at it more on a molecular and cellular level," said Christopher Hill, a U. professor of biochemistry on Sundquist's research team. "What we're trying to do is understand how the virus interacts with the cellular machinery."
The five-year NIH grant will help Sundquist's lab build on its previous discovery of how HIV grabs proteins inside a cell, forms virus particles, then uses the cell's own machinery to release the particles, Hill said.
Using X-ray crystallography, a technique that shows the anatomical structure of a protein at high resolution, the U. team will try to unravel how virus particles interact with the cell's proteins and "how that is used to get out of, or into, or move within the cell," Hill said.
HIV, another name for the human immunodeficiency virus, causes AIDS, a disease in which the body's immune system breaks down.
Last year, 103 cases of HIV were reported in the state; the Utah Department of Health anticipates between 85 and 115 HIV infections - and between 45 and 75 AIDS cases - will be reported this year.
Understanding the virus' structure could lead to the development of new types of drugs to treat the infection, as well as serve as a model system for studying how other human viruses interact with host cells.
"Obviously, we would love to be part of an effort that leads to a new therapy. That is something we think about quite a lot," Hill said.
Work at the U. center could profoundly improve how HIV infection is treated, said Ravi Basavappa, a program director for the NIH.
"HIV is extremely adept at evolving resistance against therapeutics that target individual HIV proteins," Basavappa said in a statement. "The research proposed by Dr. Sundquist and his colleagues to understand in detail how the virus interacts with components of the cell could provide a framework for developing entirely new classes of therapeutics."
The U. center will be one of only three in the country. The NIH also awarded grants to the University of California-San Francisco and the University of Pittsburgh, which will study other aspects of the virus.
The U. investigators working with Sundquist include Hill; Michael S. Kay, an assistant professor of biochemistry; David G. Myszka, a research associate professor of biochemistry; Jill Trewhella, an adjunct professor of chemistry and Gregory A. Voth, a distinguished professor of chemistry.
Other researchers who will work on Sundquist's team are from the California Institute of Technology, the Scripps Research Institute, Northwestern University and the University of Virginia.
The University of Utah's HIV Center, which will receive approximately $3.8 million in its first year of funding, will focus its research on four primary areas:
* The structure of HIV, how the virus moves within a host cell and how its RNA genome (the genetic instructions for the virus) escapes the nucleus of the host cell.
* Virus budding (or spreading) and how the virus escapes a host cell membrane.
* How HIV changes to exit a cell and enter a new cell.
* Understanding what happens immediately after HIV enters a new cell and the virus begins to replicate.
National Institutes of Health