HIV-1 gp120 JRFL effects in human MDM’s α7nAChR’s expression and functionality

According with the Joint United Nations Program on HIV/AIDS (UNAIDS), approximately 34 million of people worldwide lives with HIV, with 2.5 million new cases and 1.7 million AIDS related deaths in 2011 alone (UNAIDS, 2012). Human immune deficiency virus type 1 (HIV-1) accomplishes cell entry by direct interaction between viral envelop proteins (gp120 and gp41), and the CD4 receptor on target cells. Interaction that resulted in conformational changes to the gp120-CD4 receptor complex, enabling the virus to interact with either co-receptor, CXCR4 or CCR5 ending in gp41 mediated fusion of the viral and targeted cell membrane. Macrophages are the principal HIV-1 target cell and can be infected by M- tropic strains which use CCR5 (R5 strain) co-receptor, which is highly expressed in these cells. Analysis of newly infected individuals have shown that HIV-1 R5 (CCR5 dependent) virus strains are predominant at early infection stages. Studies in our lab using the X4 derived viral protein gp120IIIB shows that activation of the CXCR4 receptor by this virus protein increases the expression of the α7 nAChR’s resulting in CAP disruption. In this direction we are currently studying the effects of gp120 R5 strain (JRFL) in the expression of α7 nAChR’s. We hypothesized this pre-incubation of human derived macrophages (MDM’s) with gp120JRFL will affect anti-inflammatory signaling mechanism mediated by α7 nAChR’s activation. Preliminary data has showed that gp120 JRFL up-regulate α7 nAChR’s in MDM’s exposed to HIV-1 protein during 72hr. The gp120 JRFL up-regulation of the α7 nAChR in MDM’ seems to be more significant than the up-regulation shown for gp120IIIB, and can be block by the FDA approved CCR5 receptor specific antagonist maraviroc. Taken together with the recent finding that the α7 nAChR plays a major role in the control of the inflammatory response, this seems to suggest that this receptor could be used for the treatment of the persistent inflammation present in HIV patients