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

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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.

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Acknowledgments

We are very grateful for Dr. Valerie Wojna’s valuable suggestions and in depth review of this manuscript. We thank the National NeuroAIDS Tissue Consortium (NNTC) and the Data Coordinating Center (DCC) which is a project funded by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke under the following grants: U24MH100928 (California NeuroAIDS Tissue Network), U24MH100930 (Texas NeuroAIDS Research Center), and U24MH100929 (UCLA National Neurological AIDS Bank). This research was supported by the National Institutes of Health-NINDS and National Institute of General Medical Sciences (NIGMS) grants (1P20GM103642 and 2U54NS43011 to José A. Lasalde-Dominicci), the RISE Program from NIGMS (2R25GM061151 to Manuel Delgado-Vélez and Orestes Quesada), and MARC Program from NIGMS (5T34GM007821 to Orestes Quesada and Felix M. Ramos). Research reported in this publication was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number U54MD007587 and the National Institute of Mental Health (NIMH) grant Number P30MH075673-07 to Carlos A. Báez-Pagán. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Biology, University of Puerto Rico, Río Piedras Campus, San Juan, 00931-3360, Puerto Rico

    Félix M. Ramos, Manuel Delgado-Vélez, Carlos A. Báez-Pagán & José A. Lasalde-Dominicci

  2. Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, 00931-3360, Puerto Rico

    Ángel L. Ortiz

  3. Department of Physical Sciences, University of Puerto Rico, Río Piedras Campus, San Juan, 00931-3360, Puerto Rico

    Orestes Quesada

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  1. Félix M. Ramos
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  2. Manuel Delgado-Vélez
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  3. Ángel L. Ortiz
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  5. Orestes Quesada
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  6. José A. Lasalde-Dominicci
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Correspondence to Orestes Quesada or José A. Lasalde-Dominicci.

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Ramos, F.M., Delgado-Vélez, M., Ortiz, Á.L. et al. Expression of CHRFAM7A and CHRNA7 in neuronal cells and postmortem brain of HIV-infected patients: considerations for HIV-associated neurocognitive disorder. J. Neurovirol. 22, 327–335 (2016). https://doi.org/10.1007/s13365-015-0401-8

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