AIDSWEEKLY Plus; Monday, August 15, 2005
Staff Medical Writers

"We previously showed that the envelope glycoprotein from an in vitro microglia-adapted human immunodeficiency virus type 1 isolate (HIV-1(Bori)-15) is able to use lower levels of CD4 for infection and demonstrates greater exposure of the CD4-induced epitope recognized by the 17b monoclonal antibody than the envelope of its parental, peripheral isolate (HIV-1(Bori)).

"We investigated whether these phenotypic changes were related to a different interaction of their soluble monomeric gp120 proteins with CD4 or 17b. Equilibrium binding analyses showed no difference between Bori and Bori-15 gp120s," scientists writing in the Journal of Virology report.

"However, kinetic analysis of surface plasmon resonance-based, real-time binding experiments showed that while both proteins have similar association rates, Bori-15 gp120 has a statistically significant, 3-fold-lower dissociation rate from immobilized CD4 than Bori and a statistically significant, 14-fold-lower dissociation rate from 17b than Bori in the absence of soluble CD4.

"In addition," wrote J. Martin-Garcia and colleagues at the University of Pennsylvania in Philadelphia, "using the sensitivity to inhibition by anti-CD4 antibodies as a surrogate for CD4:trimeric envelope interaction, we found that Bori-15 envelope-pseudotyped viruses were significantly less sensitive than Bori pseudotypes, with 4- to 6-fold-higher 50% inhibitory concentration values for the three anti-CD4 antibodies tested."

"These differences, though small, suggest that adaptation to microglia correlates with the generation of a gp120 that forms a more stable interaction with CD4," investigators said.

"Nonetheless," the authors concluded, "the observation of limited binding changes leaves open the possibility that HIV-1 adaptation to microglia and HIV-associated dementia may be related not only to diminished CD4 dependence but also to changes in other molecular factors involved in the infection process."

Martin-Garcia and colleagues published their study in the Journal of Virology (Interaction with CD4 and antibodies to CD4-induced epitopes of the envelope gp120 from a microglial cell-adapted human immunodeficiency virus type 1 isolate. J Virol. 2005 Jun;79(11):6703-13.

Additional information can be obtained by contacting J. Martin-Garcia, University of Penn, School of Medicine, Dept. Neurology, Clinic Research Bldg, Room 274D, 415 Curie Blvd., Philadelphia, PA 19104, USA.

The publisher of the Journal of Virology can be contacted at: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: Philadelphia, Pennsylvania, United States, HIV-1-Associated Dementia, CD4 Antibodies, Microglia, Viral Pathogenesis, Viral Adaptation.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Martin-Garcia J, Cocklin S, Chaiken IM, et al., Interaction with CD4 and antibodies to CD4-induced epitopes of the envelope gp120 from a microglial cell-adapted human immunodeficiency virus type 1 isolate., J Virol. 2005 Jun;79(11):6703-13.

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