Characterization of key amino acid substitutions and dynamics of the influenza virus H3N2 hemagglutinin
(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.
(Less)
- author
- publishing date
- 2021-12
- 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}}, }