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Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages

Macrophages are long-lived target cells for HIV infection and are considered viral reservoirs. HIV assembly in macrophages occurs in virus-containing compartments (VCCs) in which virions accumulate and are stored. The regulation of the trafficking and release of these VCCs remains unknown. Using hig...

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Detalles Bibliográficos
Autores principales: Gaudin, Raphaël, Cunha de Alencar, Bruna, Jouve, Mabel, Bèrre, Stefano, Le Bouder, Emmanuel, Schindler, Michael, Varthaman, Aditi, Gobert, François-Xavier, Benaroch, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483138/
https://www.ncbi.nlm.nih.gov/pubmed/23091068
http://dx.doi.org/10.1083/jcb.201201144
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author Gaudin, Raphaël
Cunha de Alencar, Bruna
Jouve, Mabel
Bèrre, Stefano
Le Bouder, Emmanuel
Schindler, Michael
Varthaman, Aditi
Gobert, François-Xavier
Benaroch, Philippe
author_facet Gaudin, Raphaël
Cunha de Alencar, Bruna
Jouve, Mabel
Bèrre, Stefano
Le Bouder, Emmanuel
Schindler, Michael
Varthaman, Aditi
Gobert, François-Xavier
Benaroch, Philippe
author_sort Gaudin, Raphaël
collection PubMed
description Macrophages are long-lived target cells for HIV infection and are considered viral reservoirs. HIV assembly in macrophages occurs in virus-containing compartments (VCCs) in which virions accumulate and are stored. The regulation of the trafficking and release of these VCCs remains unknown. Using high resolution light and electron microscopy of HIV-1–infected primary human macrophages, we show that the spatial distribution of VCCs depended on the microtubule network and that VCC-limiting membrane was closely associated with KIF3A+ microtubules. Silencing KIF3A strongly decreased virus release from HIV-1–infected macrophages, leading to VCC accumulation intracellularly. Time-lapse microscopy further suggested that VCCs and associated KIF3A move together along microtubules. Importantly, KIF3A does not play a role in HIV release from T cells that do not possess VCCs. These results reveal that HIV-1 requires the molecular motor KIF3 to complete its cycle in primary macrophages. Targeting this step may lead to novel strategies to eliminate this viral reservoir.
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spelling pubmed-34831382013-04-29 Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages Gaudin, Raphaël Cunha de Alencar, Bruna Jouve, Mabel Bèrre, Stefano Le Bouder, Emmanuel Schindler, Michael Varthaman, Aditi Gobert, François-Xavier Benaroch, Philippe J Cell Biol Research Articles Macrophages are long-lived target cells for HIV infection and are considered viral reservoirs. HIV assembly in macrophages occurs in virus-containing compartments (VCCs) in which virions accumulate and are stored. The regulation of the trafficking and release of these VCCs remains unknown. Using high resolution light and electron microscopy of HIV-1–infected primary human macrophages, we show that the spatial distribution of VCCs depended on the microtubule network and that VCC-limiting membrane was closely associated with KIF3A+ microtubules. Silencing KIF3A strongly decreased virus release from HIV-1–infected macrophages, leading to VCC accumulation intracellularly. Time-lapse microscopy further suggested that VCCs and associated KIF3A move together along microtubules. Importantly, KIF3A does not play a role in HIV release from T cells that do not possess VCCs. These results reveal that HIV-1 requires the molecular motor KIF3 to complete its cycle in primary macrophages. Targeting this step may lead to novel strategies to eliminate this viral reservoir. The Rockefeller University Press 2012-10-29 /pmc/articles/PMC3483138/ /pubmed/23091068 http://dx.doi.org/10.1083/jcb.201201144 Text en © 2012 Gaudin et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Gaudin, Raphaël
Cunha de Alencar, Bruna
Jouve, Mabel
Bèrre, Stefano
Le Bouder, Emmanuel
Schindler, Michael
Varthaman, Aditi
Gobert, François-Xavier
Benaroch, Philippe
Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages
title Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages
title_full Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages
title_fullStr Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages
title_full_unstemmed Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages
title_short Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages
title_sort critical role for the kinesin kif3a in the hiv life cycle in primary human macrophages
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483138/
https://www.ncbi.nlm.nih.gov/pubmed/23091068
http://dx.doi.org/10.1083/jcb.201201144
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