IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.

To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required...

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Autores principales:	Eric M Feeley, Jennifer S Sims, Sinu P John, Christopher R Chin, Thomas Pertel, Li-Mei Chen, Gaurav D Gaiha, Bethany J Ryan, Ruben O Donis, Stephen J Elledge, Abraham L Brass
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/79b4c2d4af1b4f7d9ea4310cc58480f8
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spelling	oai:doaj.org-article:79b4c2d4af1b4f7d9ea4310cc58480f82021-11-18T06:05:12ZIFITM3 inhibits influenza A virus infection by preventing cytosolic entry.1553-73661553-737410.1371/journal.ppat.1002337https://doaj.org/article/79b4c2d4af1b4f7d9ea4310cc58480f82011-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22046135/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.Eric M FeeleyJennifer S SimsSinu P JohnChristopher R ChinThomas PertelLi-Mei ChenGaurav D GaihaBethany J RyanRuben O DonisStephen J ElledgeAbraham L BrassPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 10, p e1002337 (2011)
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 Eric M Feeley Jennifer S Sims Sinu P John Christopher R Chin Thomas Pertel Li-Mei Chen Gaurav D Gaiha Bethany J Ryan Ruben O Donis Stephen J Elledge Abraham L Brass IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.
description	To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats.
format	article
author	Eric M Feeley Jennifer S Sims Sinu P John Christopher R Chin Thomas Pertel Li-Mei Chen Gaurav D Gaiha Bethany J Ryan Ruben O Donis Stephen J Elledge Abraham L Brass
author_facet	Eric M Feeley Jennifer S Sims Sinu P John Christopher R Chin Thomas Pertel Li-Mei Chen Gaurav D Gaiha Bethany J Ryan Ruben O Donis Stephen J Elledge Abraham L Brass
author_sort	Eric M Feeley
title	IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.
title_short	IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.
title_full	IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.
title_fullStr	IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.
title_full_unstemmed	IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.
title_sort	ifitm3 inhibits influenza a virus infection by preventing cytosolic entry.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/79b4c2d4af1b4f7d9ea4310cc58480f8
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IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.

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