P&S Journal: Spring 1995, Vol.15, No.2
Research & Reports
Vulnerability in AIDS Virus
A recent discovery could lead to the development of drugs that could block HIV-1 infection. Researchers may have found a vulnerable point in the AIDS virus's ability to infect cells. To be infectious, HIV-1 must contain a special protein it takes from human cells. Drugs that block the incorporation of the protein may incapacitate the virus.
HIV-1's major structural protein, Gag, snatches cyclophilin A, a common cellular protein, from inside infected cells and incorporates it into mature virus. Without cyclophilin A, disabled HIV-1 cannot infect cells. Dr. Jeremy Luban, assistant professor of medicine, was lead author of the research reported in a November issue of Nature.
The research team identified the precise region on HIV-1's Gag that allows it to bind cyclophilin A and changed the Gag protein to make one amino acid different. They discovered that the mutated Gag could no longer bind cyclophilin A and the resulting mutant virus was not infectious. Certain drugs prevent the virus's uptake of cyclophilin A and make the virus unable to kill cells in culture. Dr. Luban says agents that specifically interfere with the interaction of cyclophilin A and Gag would make good candidates for new antiviral therapies.
In tissue culture, researchers showed that cyclosporin A, an immunosuppressant used to prevent tissue rejection in organ transplantation, can prevent the inclusion of cyclophilin A into the virus and render it non-infectious. However, using cyclosporin A to treat patients infected with HIV-1 would mean giving an immunosuppressant to an immunocompromised person.
Researchers from other institutions have reported on compounds related to cyclosporin A but without immunosuppressant activity that also stop viral replication. Dr. Luban's group has had similar unpublished findings with cyclosporin-like agents, but clinical trials are needed to determine anti-HIV effects in humans.