title: Expression of CHRFAM7A and CHRNA7 in neuronal cells and postmortem brain of HIV-infected patients: considerations for HIV-associated neurocognitive disorder.
abstract: 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 gp120IIIB 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 gp120IIIB 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 gp120IIIB. 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.
authors.affiliation: Department of Biology, University of Puerto Rico, Río Piedras Campus, San Juan, 00931-3360, Puerto Rico.
authors.forename: Félix M
authors.initials: FM
authors.lastname: Ramos
authors.affiliation: Department of Biology, University of Puerto Rico, Río Piedras Campus, San Juan, 00931-3360, Puerto Rico.
authors.forename: Manuel
authors.initials: M
authors.lastname: Delgado-Vélez
authors.affiliation: Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, 00931-3360, Puerto Rico.
authors.forename: Ángel L
authors.initials: ÁL
authors.lastname: Ortiz
authors.affiliation: Department of Biology, University of Puerto Rico, Río Piedras Campus, San Juan, 00931-3360, Puerto Rico.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Báez-Pagán
authors.affiliation: Department of Physical Sciences, University of Puerto Rico, Río Piedras Campus, San Juan, 00931-3360, Puerto Rico. quesada.orestes@gmail.com.
authors.forename: Orestes
authors.initials: O
authors.lastname: Quesada
authors.affiliation: Department of Biology, University of Puerto Rico, Río Piedras Campus, San Juan, 00931-3360, Puerto Rico. jlasalde@gmail.com.
authors.forename: José A
authors.initials: JA
authors.lastname: Lasalde-Dominicci
mesh_terms: D015526:AIDS Dementia Complex / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D000328:Adult; D001344:Autopsy; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology / Q000821:virology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: C579167:Chrna7 protein, human; D015699:HIV Envelope Protein gp120; D064569:alpha7 Nicotinic Acetylcholine Receptor; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: CHRFAM7A; CHRNA7; HAND; HIV; Nicotinic acetylcholine receptor; gp120