Expression of CHRFAM7A and CHRNA7 in neuronal cells and postmortem brain of HIV-infected patients: considerations for HIV-associated neurocognitive disorder
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...
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Published in | Journal of neurovirology Vol. 22; no. 3; pp. 327 - 335 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.06.2016
|
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1355-0284 1538-2443 |
DOI: | 10.1007/s13365-015-0401-8 |