Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage

Abstract HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are needed. The cellular transcription factor KAP...

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Autores principales:	Amina Ait-Ammar, Maxime Bellefroid, Fadoua Daouad, Valérie Martinelli, Jeanne Van Assche, Clémentine Wallet, Anthony Rodari, Marco De Rovere, Birthe Fahrenkrog, Christian Schwartz, Carine Van Lint, Virginie Gautier, Olivier Rohr
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe46ec113a36484184b8fb43f3c5fa39
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spelling	oai:doaj.org-article:fe46ec113a36484184b8fb43f3c5fa392021-12-02T13:57:25ZInhibition of HIV-1 gene transcription by KAP1 in myeloid lineage10.1038/s41598-021-82164-w2045-2322https://doaj.org/article/fe46ec113a36484184b8fb43f3c5fa392021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82164-whttps://doaj.org/toc/2045-2322Abstract HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are needed. The cellular transcription factor KAP1 is known as a potent repressor of gene transcription. Here we report that KAP1 represses HIV-1 gene expression in myeloid cells including microglial cells, the major reservoir of the central nervous system. Mechanistically, KAP1 interacts and colocalizes with the viral transactivator Tat to promote its degradation via the proteasome pathway and repress HIV-1 gene expression. In myeloid models of latent HIV-1 infection, the depletion of KAP1 increased viral gene elongation and reactivated HIV-1 expression. Bound to the latent HIV-1 promoter, KAP1 associates and cooperates with CTIP2, a key epigenetic silencer of HIV-1 expression in microglial cells. In addition, Tat and CTIP2 compete for KAP1 binding suggesting a dynamic modulation of the KAP1 cellular partners upon HIV-1 infection. Altogether, our results suggest that KAP1 contributes to the establishment and the persistence of HIV-1 latency in myeloid cells.Amina Ait-AmmarMaxime BellefroidFadoua DaouadValérie MartinelliJeanne Van AsscheClémentine WalletAnthony RodariMarco De RovereBirthe FahrenkrogChristian SchwartzCarine Van LintVirginie GautierOlivier RohrNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amina Ait-Ammar Maxime Bellefroid Fadoua Daouad Valérie Martinelli Jeanne Van Assche Clémentine Wallet Anthony Rodari Marco De Rovere Birthe Fahrenkrog Christian Schwartz Carine Van Lint Virginie Gautier Olivier Rohr Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage
description	Abstract HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are needed. The cellular transcription factor KAP1 is known as a potent repressor of gene transcription. Here we report that KAP1 represses HIV-1 gene expression in myeloid cells including microglial cells, the major reservoir of the central nervous system. Mechanistically, KAP1 interacts and colocalizes with the viral transactivator Tat to promote its degradation via the proteasome pathway and repress HIV-1 gene expression. In myeloid models of latent HIV-1 infection, the depletion of KAP1 increased viral gene elongation and reactivated HIV-1 expression. Bound to the latent HIV-1 promoter, KAP1 associates and cooperates with CTIP2, a key epigenetic silencer of HIV-1 expression in microglial cells. In addition, Tat and CTIP2 compete for KAP1 binding suggesting a dynamic modulation of the KAP1 cellular partners upon HIV-1 infection. Altogether, our results suggest that KAP1 contributes to the establishment and the persistence of HIV-1 latency in myeloid cells.
format	article
author	Amina Ait-Ammar Maxime Bellefroid Fadoua Daouad Valérie Martinelli Jeanne Van Assche Clémentine Wallet Anthony Rodari Marco De Rovere Birthe Fahrenkrog Christian Schwartz Carine Van Lint Virginie Gautier Olivier Rohr
author_facet	Amina Ait-Ammar Maxime Bellefroid Fadoua Daouad Valérie Martinelli Jeanne Van Assche Clémentine Wallet Anthony Rodari Marco De Rovere Birthe Fahrenkrog Christian Schwartz Carine Van Lint Virginie Gautier Olivier Rohr
author_sort	Amina Ait-Ammar
title	Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage
title_short	Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage
title_full	Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage
title_fullStr	Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage
title_full_unstemmed	Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage
title_sort	inhibition of hiv-1 gene transcription by kap1 in myeloid lineage
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fe46ec113a36484184b8fb43f3c5fa39
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Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage

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