June 7, 2004
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 Actas de la Academia Nacional de Ciencias.
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.”
El Instituto Salk de Estudios Biológicos en La Jolla, California, es una organización independiente sin fines de lucro dedicada a descubrimientos fundamentales en las ciencias de la vida, la mejora de la salud humana y la formación de futuras generaciones de investigadores. Jonas Salk, M.D., cuya vacuna contra la polio prácticamente erradicó la debilitante enfermedad de la poliomielitis en 1955, inauguró el Instituto en 1965 con un donativo de terrenos de la Ciudad de San Diego y el apoyo financiero de la March of Dimes.
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