HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases

Abstract HIV-1 co-opts several host machinery to generate a permissive environment for viral replication and transmission. In this work we reveal how HIV-1 impacts the host translation and intracellular vesicular trafficking machineries for protein synthesis and to impede the physiological late endo...

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Autores principales:	Alessandro Cinti, Valerie Le Sage, Miroslav P. Milev, Fernando Valiente-Echeverría, Christina Crossie, Marie-Joelle Miron, Nelly Panté, Martin Olivier, Andrew J. Mouland
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/12b9328987c2422886cdbc8d51c8c04b
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spelling	oai:doaj.org-article:12b9328987c2422886cdbc8d51c8c04b2021-12-02T16:08:00ZHIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases10.1038/s41598-017-05410-02045-2322https://doaj.org/article/12b9328987c2422886cdbc8d51c8c04b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05410-0https://doaj.org/toc/2045-2322Abstract HIV-1 co-opts several host machinery to generate a permissive environment for viral replication and transmission. In this work we reveal how HIV-1 impacts the host translation and intracellular vesicular trafficking machineries for protein synthesis and to impede the physiological late endosome/lysosome (LEL) trafficking in stressful conditions. First, HIV-1 enhances the activity of the master regulator of protein synthesis, the mammalian target of rapamycin (mTOR). Second, the virus commandeers mTOR-associated late endosome/lysosome (LEL) trafficking and counteracts metabolic and environmental stress-induced intracellular repositioning of LEL. We then show that the small Rag GTPases, RagA and RagB, are required for the HIV-1-mediated LEL repositioning that is likely mediated by interactions between the Rags and the viral proteins, Gag and Vif. siRNA-mediated depletion of RagA and RagB leads to a loss in mTOR association to LEL and to a blockade of viral particle assembly and release at the plasma membrane with a marked concomitant reduction in virus production. These results show that HIV-1 co-opts fundamental mechanisms that regulate LEL motility and positioning and support the notion that LEL positioning is critical for HIV-1 replication.Alessandro CintiValerie Le SageMiroslav P. MilevFernando Valiente-EcheverríaChristina CrossieMarie-Joelle MironNelly PantéMartin OlivierAndrew J. MoulandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alessandro Cinti Valerie Le Sage Miroslav P. Milev Fernando Valiente-Echeverría Christina Crossie Marie-Joelle Miron Nelly Panté Martin Olivier Andrew J. Mouland HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases
description	Abstract HIV-1 co-opts several host machinery to generate a permissive environment for viral replication and transmission. In this work we reveal how HIV-1 impacts the host translation and intracellular vesicular trafficking machineries for protein synthesis and to impede the physiological late endosome/lysosome (LEL) trafficking in stressful conditions. First, HIV-1 enhances the activity of the master regulator of protein synthesis, the mammalian target of rapamycin (mTOR). Second, the virus commandeers mTOR-associated late endosome/lysosome (LEL) trafficking and counteracts metabolic and environmental stress-induced intracellular repositioning of LEL. We then show that the small Rag GTPases, RagA and RagB, are required for the HIV-1-mediated LEL repositioning that is likely mediated by interactions between the Rags and the viral proteins, Gag and Vif. siRNA-mediated depletion of RagA and RagB leads to a loss in mTOR association to LEL and to a blockade of viral particle assembly and release at the plasma membrane with a marked concomitant reduction in virus production. These results show that HIV-1 co-opts fundamental mechanisms that regulate LEL motility and positioning and support the notion that LEL positioning is critical for HIV-1 replication.
format	article
author	Alessandro Cinti Valerie Le Sage Miroslav P. Milev Fernando Valiente-Echeverría Christina Crossie Marie-Joelle Miron Nelly Panté Martin Olivier Andrew J. Mouland
author_facet	Alessandro Cinti Valerie Le Sage Miroslav P. Milev Fernando Valiente-Echeverría Christina Crossie Marie-Joelle Miron Nelly Panté Martin Olivier Andrew J. Mouland
author_sort	Alessandro Cinti
title	HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases
title_short	HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases
title_full	HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases
title_fullStr	HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases
title_full_unstemmed	HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases
title_sort	hiv-1 enhances mtorc1 activity and repositions lysosomes to the periphery by co-opting rag gtpases
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/12b9328987c2422886cdbc8d51c8c04b
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HIV-1 enhances mTORC1 activity and repositions lysosomes to the periphery by co-opting Rag GTPases

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