New Center Receives $20 Million to Shed Light on HIV Drug Resistance

By Mika Ono

The Scripps Research Institute has received a grant totaling approximately $20 million over five years from the National Institutes of Health to research the development of drug resistance in HIV, the virus that causes AIDS.

The grant will create a new consortium, the HIV Interaction and Viral Evolution (HIVE) Center, to better understand drug resistance and lay the groundwork for developing new anti-HIV treatments.

“We’re excited about the project,” said Scripps Research Professor Arthur Olson, who is principal investigator of the new center. “Using HIV, we aim to develop a broad methodology to develop drugs in the context of the evolution of drug resistance. In the process, we’ll pursue any new anti-HIV drug, combination, or approach we find that is robust in the face of drug resistance as a potential treatment regimen.”

"This center brings together an impressive team of virologists and structural biologists to investigate the structure and function of HIV, including how it responds to the selective pressure imposed by the drugs used in AIDS therapy," said Michael Sakalian, the official who oversees the grant at the NIH National Institute of General Medical Sciences, which made the award with the National Institute of Allergy and Infectious Diseases. "Their efforts, which focus on elements of the virus that have been difficult to study, will further our understanding of host-pathogen interactions and ways to combat drug resistance."

The current effort grew out of Olson’s 15 years of research on HIV protease, a viral enzyme that is a target for several anti-HIV drugs. While the laboratory had been making progress on this avenue of research, Olson realized that all three of the virus’s enzymes—protease, integrase, and reverse transcriptase—were interacting as the virus mutated.

“A virus is a complex system, especially HIV, and there are all kinds of interplay between different drug targets,” noted Olson. “There’s a lot we don’t know about how these enzymes interact with each other, other proteins, and human proteins.”

To help fill in these gaps, Olson decided to propose a center to look at the evolution of resistance in the life cycle of the entire virus. He began reaching out to researchers with complementary specialties in the field of HIV research.

The result is a group of top researchers from across the country who will collaborate as part of the HIVE Center. The team includes: Edward Arnold, Ronald Levy, Roger Jones, and Joseph Marcotrigiano of Rutgers University; Alan N. Engelman of the Dana Farber Cancer Institute; Michael Parniak of the University of Pittsburgh; Mamuka Kvaratskhelia of Ohio State University; Alan Rein and Stephen Hughes of the National Cancer Institute-Frederick; and Richard K. Belew of Electronic Artifacts.

The group also includes scientists from both the Florida and California campuses of Scripps Research. On the California campus, joining the center will be David Goodsell, Bruce E. Torbett, Charles D. Stout, Vadim Cherezov, John Elder, and Valery V. Fokin. Contributing expertise from the Florida campus will be Patrick Griffin and Douglas Kojetin.

Olson notes the center will also draw on a clinical component that provides access to records and samples from active-duty military personnel receiving HIV treatment. This will enable the scientists to track changes in the evolution of the viral population under different conditions, including a change in treatment regimen.

The NIH project is award number for the grant is P50GM103368.

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