Rutgers cell biologist sees new HIV treatment potential in protein discovery

NEW BRUNSWICK/PISCATAWAY, N.J. – Rutgers cell biologist Bonnie L. Firestein is charting a new course in the search for an effective AIDS treatment. Firestein and her colleagues have identified a protein known as HP68 that is critical to the formation of the AIDS virus' outer shell or capsid. Treatments that target this protein could stop HIV production while avoiding the severe side effects found with current treatments.

Firestein, an assistant professor in Rutgers' department of cell biology and neuroscience, and Jaisri Lingappa, assistant professor of pathobiology at the University of Washington, are the co-principal investigators on this project.

"The identification of this protein by members of Dr. Jaisri Lingappa's laboratory, with whom I collaborated, is particularly exciting since it opens up new avenues for the treatment of HIV infection and, potentially, AIDS," said Firestein.

HIV belongs to a class of viruses, called retroviruses, which have genes made of RNA (as opposed to other organisms, such as humans, that have DNA), explained Firestein. Since HIV does not have DNA, it must infect a host cell where RNA can be made into DNA. In order for HIV to be infectious, a number of processes must occur, one of which is the assembly of Gag (group-specific antigens) proteins into a shell or capsid that protects the HIV.

The newly identified protein, designated HP68 because it is a host protein with a weight of 68 kiloDaltons (units of atomic mass), is found in normal cells in human and monkeys and other animals.

"When the cell is infected with HIV, HP68 temporarily associates with the Gag protein and helps it to form the capsid," said Firestein. "If HP68 is mutated or absent, HIV capsids do not form, and hence, HIV cannot infect other cells."

Current treatments use drugs that either stop the production of HIV RNA into DNA or interrupt virus production, but these drugs often have severe side effects. "The identification of HP68 will allow us to develop drugs that interrupt its interaction with Gag, and therefore stop HIV production," said Firestein. "Since we may be able to develop drugs that are specific for HP68, we may be able to avoid the intolerable side effects found with the drugs currently used in other courses of treatment."

Other scientists in the laboratory at the University of Washington and at the University of California at San Francisco were also involved in this research project. The results of the research appear in the Jan. 3 issue of the journal Nature as "Identification of a host protein essential for assembly of immature HIV-1 capsids."

The research was supported by the National Institutes of Health AIDS Division and the Pediatric Aids Foundation.

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