Upregulation of the alpha7 nAChR in human macrophages is induced by chronic treatment with HIV‐1 envelope protein, gp120

Abstract

Human immunodeficiency virus type‐1 (HIV‐1) infection is the commonest cause of dementia in adults less than 40 years. The cellular and molecular alterations that result in synaptic dysfunction, neuronal degeneration and cell death due to HIV‐associated dementia (HAD) by HIV‐1 infection appears to be caused by the infection of macrophages, microglia or by stem cells. We examined the effects of gp120 on the upregulation of the alpha7 nAChR expressed in human macrophages. Compared to controls, chronic treatment with gp120 showed a remarkable increase in the expression of the α7 nAChR with an increase in the concentration of gp120. In addition, macrophages chronically exposed to gp120 showed an increase the macroscopic whole‐cell currents compared to controls. After chronic exposure to gp120, macrophages also presented an increase in calcium uptake compared to non‐treated macrophages. Interestingly, experiments in several cell lines showed a similar up‐regulation of the α7 AChRs, suggesting that the up‐regulation could be occurring through a direct mechanism. We are currently conducting polysome analysis in continuous sucrose gradients to determine whether treatment with gp120 enhances the α7 nAChR mRNA association with the translational machinery. This notable up‐regulation of the α7 nAChR induced by the gp120 may be critical to the functional state of macrophages. Our data suggests that the α7 nAChR could be a key player in the HIV pathogenesis.This research work was supported by NIH GM008224, 2R01GM56371–11, NCRR 1S0RR13705 and by NIH SNRP‐U54NS4301 to JAL‐D. Also supported by NIH U54 Award CA96297–03 and NIH S06‐GM008102–3052. M.I.L is supported by RISE Award 2R25GM61151.