Gp120 envelope glycoproteins of HIV-1 Group M Subtype A and Subtype B differentially affect gene expression in human vascular endothelial cells

Abstract

Abstract While HIV-1 Group M Subtype B is the most prevalent subtype in western countries, the majority of HIV-1 infections in eastern Africa and former Soviet Union countries are caused by Subtype A. However, most of the research on HIV has focused on Subtype B and information on the molecular mechanisms of Subtype A is virtually non-existent. The lack of such knowledge results in health disparities for the development of therapeutic strategies to prevent/treat HIV-associated complications. The present study examined envelope glycoprotein (gp120) of HIV-1 Group M Subtypes A and B. The amino acid sequence alignment analysis determined that gp120 proteins of A and B subtypes are 76% identical and share 86% similarity. The treatment of human vascular endothelial cells with the two gp120 proteins exhibited differential gene expression changes as determined by Proteome Profiler Arrays. Subtype A more potently downregulated prostasin, matrix metalloproteinase-2 (MMP-2), and receptor tyrosine-protein kinase erbB-3/Her3 than did Subtype B, while Subtype B was more effective in downregulating monocyte chemoattractant proteins (MCP-2 and MCP-3). Further, epidermal growth factor (EGF), a mediator of vascular complications, was found to be upregulated by gp120 of Subtype A, but not Subtype B. This is the first report of gp120 proteins affecting human host cells in an HIV subtype-specific manner, opening up the possibility that complications may occur differently in HIV patients throughout the world. Supported by grants from NIH (R21 AG73919, R03 AG71596)