Rab11a mediates cell-cell spread and reassortment of influenza A virus genomes via tunneling nanotubes.

Influenza A virus [IAV] genomes comprise eight negative strand RNAs packaged into virions in the form of viral ribonucleoproteins [vRNPs]. Rab11a plays a crucial role in the transport of vRNPs from the nucleus to the plasma membrane via microtubules, allowing assembly and virus production. Here, we...

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Autores principales:	Ketaki Ganti, Julianna Han, Balaji Manicassamy, Anice C Lowen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/94c024f6533d41b39114d70db168e97c
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spelling	oai:doaj.org-article:94c024f6533d41b39114d70db168e97c2021-12-02T20:00:14ZRab11a mediates cell-cell spread and reassortment of influenza A virus genomes via tunneling nanotubes.1553-73661553-737410.1371/journal.ppat.1009321https://doaj.org/article/94c024f6533d41b39114d70db168e97c2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009321https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Influenza A virus [IAV] genomes comprise eight negative strand RNAs packaged into virions in the form of viral ribonucleoproteins [vRNPs]. Rab11a plays a crucial role in the transport of vRNPs from the nucleus to the plasma membrane via microtubules, allowing assembly and virus production. Here, we identify a novel function for Rab11a in the inter-cellular transport of IAV vRNPs using tunneling nanotubes [TNTs]as molecular highways. TNTs are F-Actin rich tubules that link the cytoplasm of nearby cells. In IAV-infected cells, Rab11a was visualized together with vRNPs in these actin-rich intercellular connections. To better examine viral spread via TNTs, we devised an infection system in which conventional, virion-mediated, spread was not possible. Namely, we generated HA-deficient reporter viruses which are unable to produce progeny virions but whose genomes can be replicated and trafficked. In this system, vRNP transfer to neighboring cells was observed and this transfer was found to be dependent on both actin and Rab11a. Generation of infectious virus via TNT transfer was confirmed using donor cells infected with HA-deficient virus and recipient cells stably expressing HA protein. Mixing donor cells infected with genetically distinct IAVs furthermore revealed the potential for Rab11a and TNTs to serve as a conduit for genome mixing and reassortment in IAV infections. These data therefore reveal a novel role for Rab11a in the IAV life cycle, which could have significant implications for within-host spread, genome reassortment and immune evasion.Ketaki GantiJulianna HanBalaji ManicassamyAnice C LowenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009321 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ketaki Ganti Julianna Han Balaji Manicassamy Anice C Lowen Rab11a mediates cell-cell spread and reassortment of influenza A virus genomes via tunneling nanotubes.
description	Influenza A virus [IAV] genomes comprise eight negative strand RNAs packaged into virions in the form of viral ribonucleoproteins [vRNPs]. Rab11a plays a crucial role in the transport of vRNPs from the nucleus to the plasma membrane via microtubules, allowing assembly and virus production. Here, we identify a novel function for Rab11a in the inter-cellular transport of IAV vRNPs using tunneling nanotubes [TNTs]as molecular highways. TNTs are F-Actin rich tubules that link the cytoplasm of nearby cells. In IAV-infected cells, Rab11a was visualized together with vRNPs in these actin-rich intercellular connections. To better examine viral spread via TNTs, we devised an infection system in which conventional, virion-mediated, spread was not possible. Namely, we generated HA-deficient reporter viruses which are unable to produce progeny virions but whose genomes can be replicated and trafficked. In this system, vRNP transfer to neighboring cells was observed and this transfer was found to be dependent on both actin and Rab11a. Generation of infectious virus via TNT transfer was confirmed using donor cells infected with HA-deficient virus and recipient cells stably expressing HA protein. Mixing donor cells infected with genetically distinct IAVs furthermore revealed the potential for Rab11a and TNTs to serve as a conduit for genome mixing and reassortment in IAV infections. These data therefore reveal a novel role for Rab11a in the IAV life cycle, which could have significant implications for within-host spread, genome reassortment and immune evasion.
format	article
author	Ketaki Ganti Julianna Han Balaji Manicassamy Anice C Lowen
author_facet	Ketaki Ganti Julianna Han Balaji Manicassamy Anice C Lowen
author_sort	Ketaki Ganti
title	Rab11a mediates cell-cell spread and reassortment of influenza A virus genomes via tunneling nanotubes.
title_short	Rab11a mediates cell-cell spread and reassortment of influenza A virus genomes via tunneling nanotubes.
title_full	Rab11a mediates cell-cell spread and reassortment of influenza A virus genomes via tunneling nanotubes.
title_fullStr	Rab11a mediates cell-cell spread and reassortment of influenza A virus genomes via tunneling nanotubes.
title_full_unstemmed	Rab11a mediates cell-cell spread and reassortment of influenza A virus genomes via tunneling nanotubes.
title_sort	rab11a mediates cell-cell spread and reassortment of influenza a virus genomes via tunneling nanotubes.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/94c024f6533d41b39114d70db168e97c
work_keys_str_mv	AT ketakiganti rab11amediatescellcellspreadandreassortmentofinfluenzaavirusgenomesviatunnelingnanotubes AT juliannahan rab11amediatescellcellspreadandreassortmentofinfluenzaavirusgenomesviatunnelingnanotubes AT balajimanicassamy rab11amediatescellcellspreadandreassortmentofinfluenzaavirusgenomesviatunnelingnanotubes AT aniceclowen rab11amediatescellcellspreadandreassortmentofinfluenzaavirusgenomesviatunnelingnanotubes
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Rab11a mediates cell-cell spread and reassortment of influenza A virus genomes via tunneling nanotubes.

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