Expression of CHRFAM7A and CHRNA7 in neuronal cells and postmortem brain of HIV-infected patients: considerations for HIV-associated neurocognitive disorder

• Published in: Journal of neurovirology Vol. 22; no. 3; pp. 327 - 335
• Main Authors: Ramos, Félix M., Delgado-Vélez, Manuel, Ortiz, Ángel L., Báez-Pagán, Carlos A., Quesada, Orestes, Lasalde-Dominicci, José A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2016
• Subjects: Adult; AIDS Dementia Complex - genetics; AIDS Dementia Complex - metabolism; AIDS Dementia Complex - pathology; AIDS Dementia Complex - virology; alpha7 Nicotinic Acetylcholine Receptor - genetics; alpha7 Nicotinic Acetylcholine Receptor - metabolism; Autopsy; Basal Ganglia - metabolism; Basal Ganglia - pathology; Basal Ganglia - virology; Biomedical and Life Sciences; Biomedicine; Brain - metabolism; Brain - pathology; Brain - virology; Cell Death - drug effects; Cell Line, Tumor; Female; Gene Expression Regulation; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - metabolism; HIV Envelope Protein gp120 - pharmacology; HIV-1 - genetics; HIV-1 - metabolism; HIV-1 - pathogenicity; Host-Pathogen Interactions; Human immunodeficiency virus 1; Humans; Immunology; Infectious Diseases; Lentivirus; Male; Middle Aged; Neurology; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neurosciences; Retroviridae; Severity of Illness Index; Signal Transduction; Virology; gp120; CHRFAM7A; HIV; CHRNA7; HAND; Nicotinic acetylcholine receptor
• DOI: 10.1007/s13365-015-0401-8
• ISSN: 1355-0284

Despite the recent advances in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1) remains a global health threat. HIV-1 affects the central nervous system by releasing viral proteins that trigger neuronal death and 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 patterns 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 downregulation of CHRFAM7A in neuronal cells when exposed to pathophysiological concentrations of gp120 IIIB . Our results suggest a dysregulation of CHRFAM7A and CHRNA7 expressions 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.