One Amino Acid Away from AIDS
La Jolla, CA – The ability of the AIDS virus to infect one species and bypass another may hinge on a single amino acid, a Salk Institute study has found. The work builds on the knowledge that HIV, the AIDS virus that infects humans, is relatively harmless to mice and even monkeys. The study furthers understanding of how HIV infects specific species while sparing others, and may help in the eventual development of novel drugs that halt the disease.
Associate Professor Nathaniel Landau and colleagues Bärbel Schröfelbauer and Darlene Chen found that switching one amino acid in a protein that normally fends off HIV determines whether or not the virus successfully infects cells. The findings appeared in the March 16 issue of the Proceedings of the National Academy of Sciences.
The protein, called APOBEC-3G, is part of the body's defensive system and normally keeps HIV from infecting cells. HIV, however, has a hidden weapon in the form of a protein of its own called VIF (short for virion infectivity factor), which can disable APOBEC-3G and permit infection. However, VIF can block the APOBEC-3G antiviral defenses only in specific species, so AIDS viruses that infect monkeys do not normally infect humans, and human infectious HIV cannot infect cells of primates.
The single amino acid in APOBEC-3G, the team found, determined whether VIF could bind to it. In addition, Landau and his team found that VIF could not block mouse APOBEC-3G, which is why mice are immune to HIV infection.
"Vif is required for HIV-1 replication in cells, but we did not understand how one species could be infected while a different species resisted the virus," said Landau. "These findings also give us clues about how to develop new drugs that will fight AIDS by blocking the interaction of VIF with APOBEC-3G."
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.