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Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration

In addition to glial cells, HIV-1 infection occurs in multipotent human neural precursor cells (hNPCs) and induces quiescence in NPCs. HIV-1 infection of the brain alters hNPC stemness, leading to perturbed endogenous neurorestoration of the CNS following brain damage by HIV-1, compounding the sever...

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Autores principales: Fatima, M, Kumari, R, Schwamborn, J C, Mahadevan, A, Shankar, S K, Raja, R, Seth, P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832097/
https://www.ncbi.nlm.nih.gov/pubmed/26586575
http://dx.doi.org/10.1038/cdd.2015.138
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author Fatima, M
Kumari, R
Schwamborn, J C
Mahadevan, A
Shankar, S K
Raja, R
Seth, P
author_facet Fatima, M
Kumari, R
Schwamborn, J C
Mahadevan, A
Shankar, S K
Raja, R
Seth, P
author_sort Fatima, M
collection PubMed
description In addition to glial cells, HIV-1 infection occurs in multipotent human neural precursor cells (hNPCs) and induces quiescence in NPCs. HIV-1 infection of the brain alters hNPC stemness, leading to perturbed endogenous neurorestoration of the CNS following brain damage by HIV-1, compounding the severity of dementia in adult neuroAIDS cases. In pediatric neuroAIDS cases, HIV-1 infection of neural stem cell can lead to delayed developmental milestones and impaired cognition. Using primary cultures of human fetal brain-derived hNPCs, we gained novel insights into the role of a neural stem cell determinant, tripartite containing motif 32 (TRIM32), in HIV-1 Tat-induced quiescence of NPCs. Acute HIV-1 Tat treatment of hNPCs resulted in proliferation arrest but did not induce differentiation. Cellular localization and levels of TRIM32 are critical regulators of stemness of NPCs. HIV-1 Tat exposure increased nuclear localization and levels of TRIM32 in hNPCs. The in vitro findings were validated by studying TRIM32 localization and levels in frontal cortex of HIV-1-seropositive adult patients collected at post mortem as well as by infection of hNPCs by HIV-1. We observed increased percentage of cells with nuclear localization of TRIM32 in the subventricular zone (SVZ) as compared with age-matched controls. Our quest for probing into the mechanisms revealed that TRIM32 is targeted by miR-155 as downregulation of miR-155 by HIV-1 Tat resulted in upregulation of TRIM32 levels. Furthermore, miR-155 or siRNA against TRIM32 rescued HIV-1 Tat-induced quiescence in NPCs. Our findings suggest a novel molecular cascade involving miR-155 and TRIM32 leading to HIV-1 Tat-induced attenuated proliferation of hNPCs. The study also uncovered an unidentified role for miR-155 in modulating human neural stem cell proliferation, helping in better understanding of hNPCs and diseased brain.
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spelling pubmed-48320972016-05-01 Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration Fatima, M Kumari, R Schwamborn, J C Mahadevan, A Shankar, S K Raja, R Seth, P Cell Death Differ Original Paper In addition to glial cells, HIV-1 infection occurs in multipotent human neural precursor cells (hNPCs) and induces quiescence in NPCs. HIV-1 infection of the brain alters hNPC stemness, leading to perturbed endogenous neurorestoration of the CNS following brain damage by HIV-1, compounding the severity of dementia in adult neuroAIDS cases. In pediatric neuroAIDS cases, HIV-1 infection of neural stem cell can lead to delayed developmental milestones and impaired cognition. Using primary cultures of human fetal brain-derived hNPCs, we gained novel insights into the role of a neural stem cell determinant, tripartite containing motif 32 (TRIM32), in HIV-1 Tat-induced quiescence of NPCs. Acute HIV-1 Tat treatment of hNPCs resulted in proliferation arrest but did not induce differentiation. Cellular localization and levels of TRIM32 are critical regulators of stemness of NPCs. HIV-1 Tat exposure increased nuclear localization and levels of TRIM32 in hNPCs. The in vitro findings were validated by studying TRIM32 localization and levels in frontal cortex of HIV-1-seropositive adult patients collected at post mortem as well as by infection of hNPCs by HIV-1. We observed increased percentage of cells with nuclear localization of TRIM32 in the subventricular zone (SVZ) as compared with age-matched controls. Our quest for probing into the mechanisms revealed that TRIM32 is targeted by miR-155 as downregulation of miR-155 by HIV-1 Tat resulted in upregulation of TRIM32 levels. Furthermore, miR-155 or siRNA against TRIM32 rescued HIV-1 Tat-induced quiescence in NPCs. Our findings suggest a novel molecular cascade involving miR-155 and TRIM32 leading to HIV-1 Tat-induced attenuated proliferation of hNPCs. The study also uncovered an unidentified role for miR-155 in modulating human neural stem cell proliferation, helping in better understanding of hNPCs and diseased brain. Nature Publishing Group 2016-05 2015-11-20 /pmc/articles/PMC4832097/ /pubmed/26586575 http://dx.doi.org/10.1038/cdd.2015.138 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Paper
Fatima, M
Kumari, R
Schwamborn, J C
Mahadevan, A
Shankar, S K
Raja, R
Seth, P
Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration
title Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration
title_full Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration
title_fullStr Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration
title_full_unstemmed Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration
title_short Tripartite containing motif 32 modulates proliferation of human neural precursor cells in HIV-1 neurodegeneration
title_sort tripartite containing motif 32 modulates proliferation of human neural precursor cells in hiv-1 neurodegeneration
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832097/
https://www.ncbi.nlm.nih.gov/pubmed/26586575
http://dx.doi.org/10.1038/cdd.2015.138
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