Expression of CHRFAM7A and CHRNA7 in neuronal cells and post-mortem brain of HIV-infected patients: Considerations for HIV-Associated Neurocognitive Disorder

• Published in: Journal of neurovirology 2015-11, Vol.22 (3), p.327-335
• Main Authors: Ramos, Félix M., Delgado-Vélez, Manuel, Ortiz, Ángel L., Báez-Pagán, Carlos A., Quesada, Orestes, Lasalde-Dominicci, José A.
• Format: Article
• Language: English
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1007/s13365-015-0401-8

Despite the recent advances in antiretroviral therapy, HIV-1 remains a global health threat. HIV-1 affects the central nervous system by releasing viral proteins that trigger neuronal death, neuroinflammation, and promotes alterations known as HIV-associated neurocognitive disorders (HAND). This disorder is not fully understood and no specific treatments are available. Recently, we demonstrated that the HIV-1 envelope protein gp120 IIIB induces a functional upregulation of the α7-nicotinic acetylcholine receptor (α7) in neuronal cells. Furthermore, this upregulation promotes cell death that can be abrogated with receptor antagonists, suggesting that α7 may play an important role in the development of HAND. The partial duplication of the gene coding for the α7, known as CHRFAM7A , negatively regulates α7 expression but its role in HIV infection has not been studied. Hence, we studied both CHRNA7 and CHRFAM7A regulation pattern in various gp120 IIIB in vitro conditions. In addition, we measured CHRNA7 and CHRFAM7A expression levels in postmortem brain samples from patients suffering from different stages of HAND. Our results demonstrate the induction of CHRNA7 expression accompanied by a significant down-regulation of CHRFAM7A in neuronal cells when exposed to pathophysiological concentrations of gp120 IIIB . Our results suggest a dysregulation of CHRFAM7A and CHRNA7 expression in the basal ganglia from postmortem brain samples of HIV+ subjects and expand the current knowledge about the consequences of HIV infection in the brain.