AIDSWEEKLY Plus; Monday, January 26, 2009
Staff Medical Writers

NewsRx -- "In countries infected with HIV clade B, some patients develop a rapidly progressive dementia that if untreated results in death. In regions of the world infected with HIV clade C, only milder forms of cognitive impairment have been recognized," scientists in the United States report (see also HIV/AIDS Co-Infection).

"HIV-infected macrophages are the principal mediators of dementia. HIV clade C, however, efficiently infects macrophages and HIV-infected macrophages are found in the brains of clade C-infected patients. HIV-infected macrophages release Tat protein, which may act directly on neurons to cause toxicity. We found that Tat released from Tat-expressing cells was at least 1000-fold more toxic than recombinant Tat protein. We determined whether Tat could interact with NMDA receptors and whether these interactions are clade dependent. It is demonstrated that Tat binds directly to the NMDA receptor leading to excitotoxicity. The Cys 30-Cys 31 motif in Tat is critical for exciting the NMDA receptor and the Cys31Ser mutation found in clade C Tat has a significantly attenuated neurotoxic response," wrote W.X. Li and colleagues, Johns Hopkins University.

The researchers concluded: "Through molecular modeling and site-directed mutagenesis, we predict that Cys 31 disrupts the disulfide bond between Cys 744 and Cys 798 on the NR1 subunit of the NMDA receptor by directly interacting with Cys 744 leading to a free thiol group on Cys 798 and subsequent persistent activation of the NMDA receptor."

Li and colleagues published their study in the Journal of Neuroscience (NMDA Receptor Activation by HIV-Tat Protein Is Clade Dependent. J Neurosci. 2008 Nov 19;28(47):12190-8).

For additional information, contact A. Nath, Johns Hopkins University, Dept. of Neurology, 509 Pathology, 600 N Wolfe St., Baltimore, MD 21287, USA.

The publisher's contact information for the Journal of Neuroscience is: Society Neuroscience, 11 Dupont Circle, NW, Ste. 500, Washington, DC 20036, USA.

Keywords: United States, Baltimore, HIV/AIDS Co-Infection, AIDS, Acquired Immunodeficiency Syndrome, Central Nervous System Disease, Dementia, Drugs, HIV, Human Immunodeficiency Virus Neurological Disorder, Neuroscience, Nitric Oxide, Pharmaceuticals, Therapy, Treatment, Virology, Johns Hopkins University.

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

2009-01-26
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