UAB Scientists Discover New Piece of HIV Puzzle

Scientists at the University of Alabama at Birmingham (UAB) have discovered how the building blocks of HIV adjoin to form new virus in host cells. The finding opens the door for new HIV therapies aimed at preventing the virus from developing and reproducing. “Work on a potential new drug design is already under way in the lab,” said Peter Prevelige, Ph.D., professor of microbiology at UAB and lead investigator of the study. Details of the finding are published in the January 24 issue of the Journal of Molecular Biology.

February 19, 2003

BIRMINGHAM, AL — Scientists at the University of Alabama at Birmingham (UAB) have discovered how the building blocks of HIV adjoin to form new virus in host cells. The finding opens the door for new HIV therapies aimed at preventing the virus from developing and reproducing. “Work on a potential new drug design is already under way in the lab,” said Peter Prevelige, Ph.D., professor of microbiology at UAB and lead investigator of the study. Details of the finding are published in the January 24 issue of the Journal of Molecular Biology.

Prevelige likens the assembly of HIV to building a house. “When a virus enters a cell, it contains a blueprint, all the instructions necessary to create new virus,” Prevelige said. “During the building process, strands of virus protein, like lumber used to construct a house, must be cut and adjoined to create new virus. In our study, we learned how the pieces of the virus connect together.”

HIV therapies work by targeting and interfering with different steps in the lifecycle of the virus. “Some drugs may prevent it from entering the cell while others may interfere with its ability to make new virus once inside the cell,” Prevelige said. “The problem with these drugs is that for most patients on HIV therapies, the drugs tend to become less effective over time. New drugs aimed at new targets would add to the stockpile of HIV ammunition.”

Researchers used a technology called high-resolution mass spectrometry to analyze and measure the properties of particles that compose the virus’s structure. “The technology isn’t new but its use in analyzing protein structures is relatively new,” Prevelige said. “This is the first time the technology has been used to analyze HIV, which is by far the largest, most complex protein structure ever looked at this way.”

Mass spectrometry was performed at the National High Magnetic Field Laboratory at Florida State University in Tallahassee. “The process begins with immersing the whole structure in heavy water which acts as a chemical coating solution,” Prevelige said. “The structure is then blown apart and analyzed to reveal non-coated pieces, the hidden connectors that held the structure together.”

The study was funded in part by the American Foundation for AIDS Research and the National Institutes of Health. “It was a complicated problem, so it was of great interest to us in this lab,” Prevelige said. “That, along with the strengths of UAB’s Center for AIDS Research and the Comprehensive Cancer Center’s investment in mass spectrometry, made UAB the best place to do this work.”

Other UAB researchers who collaborated on the study are Jason Lanman, Ph.D., graduate assistant in the department of microbiology and lead author of the journal publication, and Stephen Barnes, Ph.D., professor of pharmacology.