Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.

Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays important roles in virus entry and assembly, and is a targe...

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Autores principales:	Helen M Wise, Edward C Hutchinson, Brett W Jagger, Amanda D Stuart, Zi H Kang, Nicole Robb, Louis M Schwartzman, John C Kash, Ervin Fodor, Andrew E Firth, Julia R Gog, Jeffery K Taubenberger, Paul Digard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3bc38a0a2aa347b38bdcccc4ca32f8e7
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spelling	oai:doaj.org-article:3bc38a0a2aa347b38bdcccc4ca32f8e72021-11-18T06:06:24ZIdentification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.1553-73661553-737410.1371/journal.ppat.1002998https://doaj.org/article/3bc38a0a2aa347b38bdcccc4ca32f8e72012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133386/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays important roles in virus entry and assembly, and is a target for antiviral drugs and vaccination. Surprisingly, M2 is not essential for virus replication in a laboratory setting, although its loss attenuates the virus. To better understand how IAV might replicate without M2, we studied the reversion mechanism of an M2-null virus. Serial passage of a virus lacking the mRNA2 splice donor site identified a single nucleotide pseudoreverting mutation, which restored growth in cell culture and virulence in mice by upregulating mRNA4 synthesis rather than by reinstating mRNA2 production. We show that mRNA4 encodes a novel M2-related protein (designated M42) with an antigenically distinct ectodomain that can functionally replace M2 despite showing clear differences in intracellular localisation, being largely retained in the Golgi compartment. We also show that the expression of two distinct ion channel proteins is not unique to laboratory-adapted viruses but, most notably, was also a feature of the 1983 North American outbreak of H5N2 highly pathogenic avian influenza virus. In identifying a 14th influenza A polypeptide, our data reinforce the unexpectedly high coding capacity of the viral genome and have implications for virus evolution, as well as for understanding the role of M2 in the virus life cycle.Helen M WiseEdward C HutchinsonBrett W JaggerAmanda D StuartZi H KangNicole RobbLouis M SchwartzmanJohn C KashErvin FodorAndrew E FirthJulia R GogJeffery K TaubenbergerPaul DigardPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 11, p e1002998 (2012)
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 Helen M Wise Edward C Hutchinson Brett W Jagger Amanda D Stuart Zi H Kang Nicole Robb Louis M Schwartzman John C Kash Ervin Fodor Andrew E Firth Julia R Gog Jeffery K Taubenberger Paul Digard Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.
description	Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays important roles in virus entry and assembly, and is a target for antiviral drugs and vaccination. Surprisingly, M2 is not essential for virus replication in a laboratory setting, although its loss attenuates the virus. To better understand how IAV might replicate without M2, we studied the reversion mechanism of an M2-null virus. Serial passage of a virus lacking the mRNA2 splice donor site identified a single nucleotide pseudoreverting mutation, which restored growth in cell culture and virulence in mice by upregulating mRNA4 synthesis rather than by reinstating mRNA2 production. We show that mRNA4 encodes a novel M2-related protein (designated M42) with an antigenically distinct ectodomain that can functionally replace M2 despite showing clear differences in intracellular localisation, being largely retained in the Golgi compartment. We also show that the expression of two distinct ion channel proteins is not unique to laboratory-adapted viruses but, most notably, was also a feature of the 1983 North American outbreak of H5N2 highly pathogenic avian influenza virus. In identifying a 14th influenza A polypeptide, our data reinforce the unexpectedly high coding capacity of the viral genome and have implications for virus evolution, as well as for understanding the role of M2 in the virus life cycle.
format	article
author	Helen M Wise Edward C Hutchinson Brett W Jagger Amanda D Stuart Zi H Kang Nicole Robb Louis M Schwartzman John C Kash Ervin Fodor Andrew E Firth Julia R Gog Jeffery K Taubenberger Paul Digard
author_facet	Helen M Wise Edward C Hutchinson Brett W Jagger Amanda D Stuart Zi H Kang Nicole Robb Louis M Schwartzman John C Kash Ervin Fodor Andrew E Firth Julia R Gog Jeffery K Taubenberger Paul Digard
author_sort	Helen M Wise
title	Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.
title_short	Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.
title_full	Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.
title_fullStr	Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.
title_full_unstemmed	Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.
title_sort	identification of a novel splice variant form of the influenza a virus m2 ion channel with an antigenically distinct ectodomain.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3bc38a0a2aa347b38bdcccc4ca32f8e7
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Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.

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