HIV takes cellular opportunities to aid infection

Scientists will have a new view of how the AIDS virus (HIV) enters a target cell and begins its process of infection, thanks to a technique created by researchers at the Salk Institute.

The technique allows scientists to observe for the first time the steps taken by viruses like HIV after they enter a cell. The study was done with a chicken virus that was modified to contain the genes of HIV. Both the chicken virus and HIV are retroviruses, which means their genomes are made from RNA rather than DNA. When the viruses enter a host cell, their RNA genomes are converted to DNA, which integrates into the DNA of the host cell. This step is essential for the formation of new virus particles.

John Young, a Salk professor of infectious disease, and colleague Shakti Narayan reported their findings in the May 18 edition of the Proceedings of the National Academy of Sciences.

The research provides new insights into the chemical events that allow viruses like HIV to replicate within cells. Scientists have long known how HIV breaks into the host cell by merging with its surface layer. They’ve also known how the viral genome is copied and can hitch onto the cell’s genetic material and begin expressing proteins that aid infection. But they didn’t know the steps in between.

“This technique shows us what happens after the virus first steps in the door, and removes its coating,” said Young. “We now know that molecules exist in cells that help the virus convert its RNA genome to DNA but we don’t yet know what those molecules are. Once we identify them, which this system allows, we may be able to manipulate them to halt viral DNA synthesis, and produce a new therapy for AIDS.” This new technique uses a test-tube system to study the chemical players in virus infectivity, thereby allowing scientists to analyze infectivity in a setting not complicated by other cellular structures.

AIDS is a major epidemic in many developing countries in Africa and Asia, and has been responsible for more than 500,000 deaths in the United States. About 47 million people worldwide are afflicted with AIDS.

AIDS is currently incurable. However, cocktails that contain chemical agents that block various steps of viral replication have allowed millions of people to survive with the disease. “This work could provide us with another class of molecules to add to the cocktail,” said Young. “Once we identify cellular factors that regulate HIV replication, we may be able devise new treatments for other viral infections, as well.”

The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. Jonas Salk, M.D., founded the institute in 1960 with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.