Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit

ABSTRACT Human antibody-based immunity to influenza A virus is limited by antigenic drift resulting from amino acid substitutions in the hemagglutinin (HA) head domain. Glycan addition can cause large antigenic changes but is limited by fitness costs to viral replication. Here, we report that glycan...

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Autores principales:	Meghan O. Altman, Matthew Angel, Ivan Košík, Nídia S. Trovão, Seth J. Zost, James S. Gibbs, Lorenzo Casalino, Rommie E. Amaro, Scott E. Hensley, Martha I. Nelson, Jonathan W. Yewdell
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	influenza viral evolution hemagglutinin immune evasion glycosylation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b7c5ac3ce6cf49fcb5e61be2761289cd
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spelling	oai:doaj.org-article:b7c5ac3ce6cf49fcb5e61be2761289cd2021-11-15T15:55:26ZHuman Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit10.1128/mBio.00204-192150-7511https://doaj.org/article/b7c5ac3ce6cf49fcb5e61be2761289cd2019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00204-19https://doaj.org/toc/2150-7511ABSTRACT Human antibody-based immunity to influenza A virus is limited by antigenic drift resulting from amino acid substitutions in the hemagglutinin (HA) head domain. Glycan addition can cause large antigenic changes but is limited by fitness costs to viral replication. Here, we report that glycans are added to H1 and H3 HAs at discrete 5-to-7-year intervals, until they reach a functional glycan limit, after which glycans are swapped at approximately 2-fold-longer intervals. Consistent with this pattern, 2009 pandemic H1N1 added a glycan at residue N162 over the 2015–2016 season, an addition that required two epistatic HA head mutations for complete glycosylation. These strains rapidly replaced H1N1 strains globally, by 2017 dominating H3N2 and influenza B virus strains for the season. The pattern of glycan modulation that we outline should aid efforts for tracing the epidemic potential of evolving human IAV strains. IMPORTANCE Frequent mutation of its major antibody target, the glycoprotein hemagglutinin, ensures that the influenza virus is perennially both a rapidly emerging virus and a major threat to public health. One type of mutation escapes immunity by adding a glycan onto an area of hemagglutinin that many antibodies recognize. This study revealed that these glycan changes follow a simple temporal pattern. Every 5 to 7 years, hemagglutinin adds a new glycan, up to a limit. After this limit is reached, no net additions of glycans occur. Instead, glycans are swapped or lost at longer intervals. Eventually, a pandemic replaces the terminally glycosylated hemagglutinin with a minimally glycosylated one from the animal reservoir, restarting the cycle. This pattern suggests the following: (i) some hemagglutinins are evolved for this decades-long process, which is both defined by and limited by successive glycan addition; and (ii) hemagglutinin's antibody dominance and its capacity for mutations are highly adapted features that allow influenza to outpace our antibody-based immunity.Meghan O. AltmanMatthew AngelIvan KošíkNídia S. TrovãoSeth J. ZostJames S. GibbsLorenzo CasalinoRommie E. AmaroScott E. HensleyMartha I. NelsonJonathan W. YewdellAmerican Society for Microbiologyarticleinfluenzaviral evolutionhemagglutininimmune evasionglycosylationMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	influenza viral evolution hemagglutinin immune evasion glycosylation Microbiology QR1-502
spellingShingle	influenza viral evolution hemagglutinin immune evasion glycosylation Microbiology QR1-502 Meghan O. Altman Matthew Angel Ivan Košík Nídia S. Trovão Seth J. Zost James S. Gibbs Lorenzo Casalino Rommie E. Amaro Scott E. Hensley Martha I. Nelson Jonathan W. Yewdell Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit
description	ABSTRACT Human antibody-based immunity to influenza A virus is limited by antigenic drift resulting from amino acid substitutions in the hemagglutinin (HA) head domain. Glycan addition can cause large antigenic changes but is limited by fitness costs to viral replication. Here, we report that glycans are added to H1 and H3 HAs at discrete 5-to-7-year intervals, until they reach a functional glycan limit, after which glycans are swapped at approximately 2-fold-longer intervals. Consistent with this pattern, 2009 pandemic H1N1 added a glycan at residue N162 over the 2015–2016 season, an addition that required two epistatic HA head mutations for complete glycosylation. These strains rapidly replaced H1N1 strains globally, by 2017 dominating H3N2 and influenza B virus strains for the season. The pattern of glycan modulation that we outline should aid efforts for tracing the epidemic potential of evolving human IAV strains. IMPORTANCE Frequent mutation of its major antibody target, the glycoprotein hemagglutinin, ensures that the influenza virus is perennially both a rapidly emerging virus and a major threat to public health. One type of mutation escapes immunity by adding a glycan onto an area of hemagglutinin that many antibodies recognize. This study revealed that these glycan changes follow a simple temporal pattern. Every 5 to 7 years, hemagglutinin adds a new glycan, up to a limit. After this limit is reached, no net additions of glycans occur. Instead, glycans are swapped or lost at longer intervals. Eventually, a pandemic replaces the terminally glycosylated hemagglutinin with a minimally glycosylated one from the animal reservoir, restarting the cycle. This pattern suggests the following: (i) some hemagglutinins are evolved for this decades-long process, which is both defined by and limited by successive glycan addition; and (ii) hemagglutinin's antibody dominance and its capacity for mutations are highly adapted features that allow influenza to outpace our antibody-based immunity.
format	article
author	Meghan O. Altman Matthew Angel Ivan Košík Nídia S. Trovão Seth J. Zost James S. Gibbs Lorenzo Casalino Rommie E. Amaro Scott E. Hensley Martha I. Nelson Jonathan W. Yewdell
author_facet	Meghan O. Altman Matthew Angel Ivan Košík Nídia S. Trovão Seth J. Zost James S. Gibbs Lorenzo Casalino Rommie E. Amaro Scott E. Hensley Martha I. Nelson Jonathan W. Yewdell
author_sort	Meghan O. Altman
title	Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit
title_short	Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit
title_full	Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit
title_fullStr	Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit
title_full_unstemmed	Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit
title_sort	human influenza a virus hemagglutinin glycan evolution follows a temporal pattern to a glycan limit
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b7c5ac3ce6cf49fcb5e61be2761289cd
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Human Influenza A Virus Hemagglutinin Glycan Evolution Follows a Temporal Pattern to a Glycan Limit

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