Antigenic Variation of Clade 2.1 H5N1 Virus Is Determined by a Few Amino Acid Substitutions Immediately Adjacent to the Receptor Binding Site

ABSTRACT Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are genetically highly variable and have diversified into multiple phylogenetic clades over the past decade. Antigenic drift is a well-studied phenomenon for seasonal human influenza viruses, but much less is known about t...

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Autores principales: Björn F. Koel, Stefan van der Vliet, David F. Burke, Theo M. Bestebroer, Eny E. Bharoto, I. Wayan W. Yasa, Inna Herliana, Brigitta M. Laksono, Kemin Xu, Eugene Skepner, Colin A. Russell, Guus F. Rimmelzwaan, Daniel R. Perez, Albert D. M. E. Osterhaus, Derek J. Smith, Teguh Y. Prajitno, Ron A. M. Fouchier
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Publicado: American Society for Microbiology 2014
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spelling oai:doaj.org-article:0f04013622194b4b9171bb12343afa882021-11-15T15:47:38ZAntigenic Variation of Clade 2.1 H5N1 Virus Is Determined by a Few Amino Acid Substitutions Immediately Adjacent to the Receptor Binding Site10.1128/mBio.01070-142150-7511https://doaj.org/article/0f04013622194b4b9171bb12343afa882014-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01070-14https://doaj.org/toc/2150-7511ABSTRACT Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are genetically highly variable and have diversified into multiple phylogenetic clades over the past decade. Antigenic drift is a well-studied phenomenon for seasonal human influenza viruses, but much less is known about the antigenic evolution of HPAI H5N1 viruses that circulate in poultry. In this study, we focused on HPAI H5N1 viruses that are enzootic to Indonesia. We selected representative viruses from genetically distinct lineages that are currently circulating and determined their antigenic properties by hemagglutination inhibition assays. At least six antigenic variants have circulated between 2003, when H5N1 clade 2.1 viruses were first detected in Indonesia, and 2011. During this period, multiple antigenic variants cocirculated in the same geographic regions. Mutant viruses were constructed by site-directed mutagenesis to represent each of the circulating antigenic variants, revealing that antigenic differences between clade 2.1 viruses were due to only one or very few amino acid substitutions immediately adjacent to the receptor binding site. Antigenic variants of H5N1 virus evaded recognition by both ferret and chicken antibodies. The molecular basis for antigenic change in clade 2.1 viruses closely resembled that of seasonal human influenza viruses, indicating that the hemagglutinin of influenza viruses from different hosts and subtypes may be similarly restricted to evade antibody recognition. IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses are responsible for severe outbreaks in both commercial and backyard poultry, causing considerable economic losses and regular zoonotic transmissions to humans. Vaccination is used increasingly to reduce the burden of HPAI H5N1 virus in poultry. Influenza viruses can escape from recognition by antibodies induced upon vaccination or infection through genetic changes in the hemagglutinin protein. The evolutionary patterns and molecular basis of antigenic change in HPAI H5N1 viruses are poorly understood, hampering formulation of optimal vaccination strategies. We have shown here that HPAI H5N1 viruses in Indonesia diversified into multiple antigenic variants, that antigenic differences were due to one or a very few substitutions near the receptor binding site, and that the molecular basis for antigenic change was remarkably similar to that for seasonal human influenza viruses. These findings have consequences for future vaccination and surveillance considerations and contribute to the understanding of the antigenic evolution of influenza viruses.Björn F. KoelStefan van der VlietDavid F. BurkeTheo M. BestebroerEny E. BharotoI. Wayan W. YasaInna HerlianaBrigitta M. LaksonoKemin XuEugene SkepnerColin A. RussellGuus F. RimmelzwaanDaniel R. PerezAlbert D. M. E. OsterhausDerek J. SmithTeguh Y. PrajitnoRon A. M. FouchierAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 3 (2014)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
Björn F. Koel
Stefan van der Vliet
David F. Burke
Theo M. Bestebroer
Eny E. Bharoto
I. Wayan W. Yasa
Inna Herliana
Brigitta M. Laksono
Kemin Xu
Eugene Skepner
Colin A. Russell
Guus F. Rimmelzwaan
Daniel R. Perez
Albert D. M. E. Osterhaus
Derek J. Smith
Teguh Y. Prajitno
Ron A. M. Fouchier
Antigenic Variation of Clade 2.1 H5N1 Virus Is Determined by a Few Amino Acid Substitutions Immediately Adjacent to the Receptor Binding Site
description ABSTRACT Highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are genetically highly variable and have diversified into multiple phylogenetic clades over the past decade. Antigenic drift is a well-studied phenomenon for seasonal human influenza viruses, but much less is known about the antigenic evolution of HPAI H5N1 viruses that circulate in poultry. In this study, we focused on HPAI H5N1 viruses that are enzootic to Indonesia. We selected representative viruses from genetically distinct lineages that are currently circulating and determined their antigenic properties by hemagglutination inhibition assays. At least six antigenic variants have circulated between 2003, when H5N1 clade 2.1 viruses were first detected in Indonesia, and 2011. During this period, multiple antigenic variants cocirculated in the same geographic regions. Mutant viruses were constructed by site-directed mutagenesis to represent each of the circulating antigenic variants, revealing that antigenic differences between clade 2.1 viruses were due to only one or very few amino acid substitutions immediately adjacent to the receptor binding site. Antigenic variants of H5N1 virus evaded recognition by both ferret and chicken antibodies. The molecular basis for antigenic change in clade 2.1 viruses closely resembled that of seasonal human influenza viruses, indicating that the hemagglutinin of influenza viruses from different hosts and subtypes may be similarly restricted to evade antibody recognition. IMPORTANCE Highly pathogenic avian influenza (HPAI) H5N1 viruses are responsible for severe outbreaks in both commercial and backyard poultry, causing considerable economic losses and regular zoonotic transmissions to humans. Vaccination is used increasingly to reduce the burden of HPAI H5N1 virus in poultry. Influenza viruses can escape from recognition by antibodies induced upon vaccination or infection through genetic changes in the hemagglutinin protein. The evolutionary patterns and molecular basis of antigenic change in HPAI H5N1 viruses are poorly understood, hampering formulation of optimal vaccination strategies. We have shown here that HPAI H5N1 viruses in Indonesia diversified into multiple antigenic variants, that antigenic differences were due to one or a very few substitutions near the receptor binding site, and that the molecular basis for antigenic change was remarkably similar to that for seasonal human influenza viruses. These findings have consequences for future vaccination and surveillance considerations and contribute to the understanding of the antigenic evolution of influenza viruses.
format article
author Björn F. Koel
Stefan van der Vliet
David F. Burke
Theo M. Bestebroer
Eny E. Bharoto
I. Wayan W. Yasa
Inna Herliana
Brigitta M. Laksono
Kemin Xu
Eugene Skepner
Colin A. Russell
Guus F. Rimmelzwaan
Daniel R. Perez
Albert D. M. E. Osterhaus
Derek J. Smith
Teguh Y. Prajitno
Ron A. M. Fouchier
author_facet Björn F. Koel
Stefan van der Vliet
David F. Burke
Theo M. Bestebroer
Eny E. Bharoto
I. Wayan W. Yasa
Inna Herliana
Brigitta M. Laksono
Kemin Xu
Eugene Skepner
Colin A. Russell
Guus F. Rimmelzwaan
Daniel R. Perez
Albert D. M. E. Osterhaus
Derek J. Smith
Teguh Y. Prajitno
Ron A. M. Fouchier
author_sort Björn F. Koel
title Antigenic Variation of Clade 2.1 H5N1 Virus Is Determined by a Few Amino Acid Substitutions Immediately Adjacent to the Receptor Binding Site
title_short Antigenic Variation of Clade 2.1 H5N1 Virus Is Determined by a Few Amino Acid Substitutions Immediately Adjacent to the Receptor Binding Site
title_full Antigenic Variation of Clade 2.1 H5N1 Virus Is Determined by a Few Amino Acid Substitutions Immediately Adjacent to the Receptor Binding Site
title_fullStr Antigenic Variation of Clade 2.1 H5N1 Virus Is Determined by a Few Amino Acid Substitutions Immediately Adjacent to the Receptor Binding Site
title_full_unstemmed Antigenic Variation of Clade 2.1 H5N1 Virus Is Determined by a Few Amino Acid Substitutions Immediately Adjacent to the Receptor Binding Site
title_sort antigenic variation of clade 2.1 h5n1 virus is determined by a few amino acid substitutions immediately adjacent to the receptor binding site
publisher American Society for Microbiology
publishDate 2014
url https://doaj.org/article/0f04013622194b4b9171bb12343afa88
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