'Search and destroy' protein turns tables on HIV

MINNEAPOLIS / ST. PAUL -- A human protein that mutates the AIDS virus (HIV) and holds potential for keeping the disease at bay has been discovered and its function described by a team led by Reuben Harris of the University of Minnesota. The new protein (called APOBEC3F) and one described previously (APOBEC3G) can directly mutate HIV. Such proteins--called retroviral restrictors--may contribute to HIV resistance in some people. Harris, an assistant professor of biochemistry, molecular biology and biophysics, and colleagues at the university report the discovery in a paper to be published online June 24 in the journal Current Biology.

In an individual infected with HIV, the virus uses the human cellular machinery to assemble new viral particles. But sometimes those particles contain time bombs: human APOBEC proteins that hitch a ride in the particles and mutate the virus' genetic material after it has infected a new host cell.

Unfortunately for us, the AIDS virus has evolved a counterdefense. It produces a protein called VIF (viral infectivity factor), which triggers the destruction of the retroviral restrictors, thereby preventing mutations from occurring. What scientists don't know is whether some HIV-resistant people have forms of the retroviral restrictor proteins that can evade VIF and avoid destruction.

When DNA from the HIV virus is inserted into the human genome, it sometimes bears the scars of encounters with the APOBEC proteins. The two proteins leave different mutational "signatures," and the signature of APOBEC3F occurs more often.

This, said Harris, indicates that it might be less vulnerable to the virus' VIF counterdefense. Indeed, using a model HIV system, Harris and colleagues showed that APOBEC3F was less susceptible to VIF than APOBEC3G. Moreover, said Harris, the two proteins can account for all the anti-HIV mutational signatures apparent in HIV DNA of AIDS patients. But what function the proteins perform in non-H

Contact: Deane Morrison
University of Minnesota

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