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Proteins in African HIV strains interact differently with drugs

Naturally occurring genetic variations in HIV-A and HIV-C, the two subtypes of HIV prevalent in Africa, make it harder for inhibitory drugs to bind to the protease, a key protein involved in viral maturation, according to a new report by biologists in The Krieger School of Arts and Sciences of The Johns Hopkins University.

Ernesto Freire, the Henry A. Walters professor of biology, emphasized that the new findings, published in The Proceedings of the National Academy of Sciences, are based on in-vitro tests of basic biochemical properties, and therefore cannot be used to assess the effectiveness of inhibitor drugs in patient treatments.

Instead, Freire suggested that the results add new support to the argument that scientists need to broaden the focus of HIV drug development, which has been almost exclusively centered on HIV-B.

"More than two-thirds of all AIDS cases today are in Africa, and those cases are predominantly HIV-A and HIV-C," says Freire. "Those different subtypes can vary genetically from the B subtype as much as 10 to 30 percent along their entire genome, and this new report proves that variation can affect interactions between drugs and HIV proteins at a very basic biochemical level. We need to broaden drug development efforts to include these subtypes."

For the research, Freire's group created recombinant forms of the proteases from HIV-A and HIV-C, using information from viral gene databases (GenBank) in Africa to recreate the proteins. HIV-A dominates in the northern part of Sub-Saharan Africa, while HIV-C is prevalent in southern regions.

Freire's lab measured the proteases' efficiency and biochemical fitness through factors related to catalysis, a chemical term for a process where one substance (the protease) accelerates a chemical reaction in another substance (the substrate) without being changed itself. The catalytic action of the protease is v
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Contact: Michael Purdy
mcp@jhu.edu
410-516-7160
Johns Hopkins University
13-May-2001


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