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Characterization of key amino acid substitutions and dynamics of the influenza virus H3N2 hemagglutinin

Wang, Maggie Haitian ; Lou, Jingzhi ; Cao, Lirong ; Zhao, Shi ; Chan, Renee Wy ; Chan, Paul Ks ; Chan, Martin Chi-Wai ; Chong, Marc Kc ; Wu, William Kk and Wei, Yuchen , et al. (2021) In Journal of Infection 83(6). p.671-677
Abstract

The annual epidemics of seasonal influenza is partly attributed to the continued virus evolution. It is challenging to evaluate the effect of influenza virus mutations on evading population immunity. In this study, we introduce a novel statistical and computational approach to measure the dynamic molecular determinants underlying epidemics using effective mutations (EMs), and account for the time of waning mutation advantage against herd immunity by measuring the effective mutation periods (EMPs). Extensive analysis is performed on the sequencing and epidemiology data of H3N2 epidemics in ten regions from season to season. We systematically identified 46 EMs in the hemagglutinin (HA) gene, in which the majority were antigenic sites.... (More)

The annual epidemics of seasonal influenza is partly attributed to the continued virus evolution. It is challenging to evaluate the effect of influenza virus mutations on evading population immunity. In this study, we introduce a novel statistical and computational approach to measure the dynamic molecular determinants underlying epidemics using effective mutations (EMs), and account for the time of waning mutation advantage against herd immunity by measuring the effective mutation periods (EMPs). Extensive analysis is performed on the sequencing and epidemiology data of H3N2 epidemics in ten regions from season to season. We systematically identified 46 EMs in the hemagglutinin (HA) gene, in which the majority were antigenic sites. Eight EMs were located in immunosubdominant stalk domain, an important target for developing broadly reactive antibodies. The EMs might provide timely information on key substitutions for influenza vaccines antigen design. The EMP suggested that major genetic variants of H3N2 circulated in Southeast Asia for an average duration of 4.5 years (SD 2.4) compared to a significantly shorter 2.0 years (SD 1.0) in temperate regions. The proposed method bridges population epidemics and molecular characteristics of infectious diseases, and would find broad applications in various pathogens mutation estimations.

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publishing date
type
Contribution to journal
publication status
published
keywords
Amino Acid Substitution, Hemagglutinin Glycoproteins, Influenza Virus/genetics, Hemagglutinins, Humans, Influenza A Virus, H3N2 Subtype/genetics, Influenza, Human/epidemiology, Phylogeny
in
Journal of Infection
volume
83
issue
6
pages
671 - 677
publisher
W.B. Saunders
external identifiers
  • scopus:85118105757
  • pmid:34627840
ISSN
1532-2742
DOI
10.1016/j.jinf.2021.09.026
language
English
LU publication?
no
additional info
Copyright © 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
id
f3bc4fab-97d4-4dcd-91aa-d0ec260bdf92
date added to LUP
2024-02-05 15:16:05
date last changed
2024-04-08 08:22:59
@article{f3bc4fab-97d4-4dcd-91aa-d0ec260bdf92,
  abstract     = {{<p>The annual epidemics of seasonal influenza is partly attributed to the continued virus evolution. It is challenging to evaluate the effect of influenza virus mutations on evading population immunity. In this study, we introduce a novel statistical and computational approach to measure the dynamic molecular determinants underlying epidemics using effective mutations (EMs), and account for the time of waning mutation advantage against herd immunity by measuring the effective mutation periods (EMPs). Extensive analysis is performed on the sequencing and epidemiology data of H3N2 epidemics in ten regions from season to season. We systematically identified 46 EMs in the hemagglutinin (HA) gene, in which the majority were antigenic sites. Eight EMs were located in immunosubdominant stalk domain, an important target for developing broadly reactive antibodies. The EMs might provide timely information on key substitutions for influenza vaccines antigen design. The EMP suggested that major genetic variants of H3N2 circulated in Southeast Asia for an average duration of 4.5 years (SD 2.4) compared to a significantly shorter 2.0 years (SD 1.0) in temperate regions. The proposed method bridges population epidemics and molecular characteristics of infectious diseases, and would find broad applications in various pathogens mutation estimations.</p>}},
  author       = {{Wang, Maggie Haitian and Lou, Jingzhi and Cao, Lirong and Zhao, Shi and Chan, Renee Wy and Chan, Paul Ks and Chan, Martin Chi-Wai and Chong, Marc Kc and Wu, William Kk and Wei, Yuchen and Zhang, Haoyang and Zee, Benny Cy and Yeoh, Eng-Kiong}},
  issn         = {{1532-2742}},
  keywords     = {{Amino Acid Substitution; Hemagglutinin Glycoproteins, Influenza Virus/genetics; Hemagglutinins; Humans; Influenza A Virus, H3N2 Subtype/genetics; Influenza, Human/epidemiology; Phylogeny}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{671--677}},
  publisher    = {{W.B. Saunders}},
  series       = {{Journal of Infection}},
  title        = {{Characterization of key amino acid substitutions and dynamics of the influenza virus H3N2 hemagglutinin}},
  url          = {{http://dx.doi.org/10.1016/j.jinf.2021.09.026}},
  doi          = {{10.1016/j.jinf.2021.09.026}},
  volume       = {{83}},
  year         = {{2021}},
}