The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.

PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with a...

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Autores principales:	Zsuzsanna T Varga, Irene Ramos, Rong Hai, Mirco Schmolke, Adolfo García-Sastre, Ana Fernandez-Sesma, Peter Palese
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/f74b89840115468bb41bf23f6754bda1
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spelling	oai:doaj.org-article:f74b89840115468bb41bf23f6754bda12021-11-18T06:03:20ZThe influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.1553-73661553-737410.1371/journal.ppat.1002067https://doaj.org/article/f74b89840115468bb41bf23f6754bda12011-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21695240/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with an asparagine (66N) at this position. Recently, we found that an influenza virus expressing PB1-F2 N66S suppresses interferon (IFN)-stimulated genes in mice. To characterize this phenomenon, we employed several in vitro assays. Overexpression of the A/Puerto Rico/8/1934 (PR8) PB1-F2 protein in 293T cells decreased RIG-I mediated activation of an IFN-β reporter and secretion of IFN as determined by bioassay. Of note, the PB1-F2 N66S protein showed enhanced IFN antagonism activity compared to PB1-F2 wildtype. Similar observations were found in the context of viral infection with a PR8 PB1-F2 N66S virus. To understand the relationship between NS1, a previously described influenza virus protein involved in suppression of IFN synthesis, and PB1-F2, we investigated the induction of IFN when NS1 and PB1-F2 were co-expressed in an in vitro transfection system. In this assay we found that PB1-F2 N66S further reduced IFN induction in the presence of NS1. By inducing the IFN-β reporter at different levels in the signaling cascade, we found that PB1-F2 inhibited IFN production at the level of the mitochondrial antiviral signaling protein (MAVS). Furthermore, immunofluorescence studies revealed that PB1-F2 co-localizes with MAVS. In summary, we have characterized the anti-interferon function of PB1-F2 and we suggest that this activity contributes to the enhanced pathogenicity seen with PB1-F2 N66S- expressing influenza viruses.Zsuzsanna T VargaIrene RamosRong HaiMirco SchmolkeAdolfo García-SastreAna Fernandez-SesmaPeter PalesePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 6, p e1002067 (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 Zsuzsanna T Varga Irene Ramos Rong Hai Mirco Schmolke Adolfo García-Sastre Ana Fernandez-Sesma Peter Palese The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.
description	PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with an asparagine (66N) at this position. Recently, we found that an influenza virus expressing PB1-F2 N66S suppresses interferon (IFN)-stimulated genes in mice. To characterize this phenomenon, we employed several in vitro assays. Overexpression of the A/Puerto Rico/8/1934 (PR8) PB1-F2 protein in 293T cells decreased RIG-I mediated activation of an IFN-β reporter and secretion of IFN as determined by bioassay. Of note, the PB1-F2 N66S protein showed enhanced IFN antagonism activity compared to PB1-F2 wildtype. Similar observations were found in the context of viral infection with a PR8 PB1-F2 N66S virus. To understand the relationship between NS1, a previously described influenza virus protein involved in suppression of IFN synthesis, and PB1-F2, we investigated the induction of IFN when NS1 and PB1-F2 were co-expressed in an in vitro transfection system. In this assay we found that PB1-F2 N66S further reduced IFN induction in the presence of NS1. By inducing the IFN-β reporter at different levels in the signaling cascade, we found that PB1-F2 inhibited IFN production at the level of the mitochondrial antiviral signaling protein (MAVS). Furthermore, immunofluorescence studies revealed that PB1-F2 co-localizes with MAVS. In summary, we have characterized the anti-interferon function of PB1-F2 and we suggest that this activity contributes to the enhanced pathogenicity seen with PB1-F2 N66S- expressing influenza viruses.
format	article
author	Zsuzsanna T Varga Irene Ramos Rong Hai Mirco Schmolke Adolfo García-Sastre Ana Fernandez-Sesma Peter Palese
author_facet	Zsuzsanna T Varga Irene Ramos Rong Hai Mirco Schmolke Adolfo García-Sastre Ana Fernandez-Sesma Peter Palese
author_sort	Zsuzsanna T Varga
title	The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.
title_short	The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.
title_full	The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.
title_fullStr	The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.
title_full_unstemmed	The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.
title_sort	influenza virus protein pb1-f2 inhibits the induction of type i interferon at the level of the mavs adaptor protein.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/f74b89840115468bb41bf23f6754bda1
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The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.

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