tetano
Editor, Senior Moderator
J Infect
. 2021 Oct 7;S0163-4453(21)00498-9.
doi: 10.1016/j.jinf.2021.09.026. Online ahead of print.
Characterization of key amino acid substitutions and dynamics of the influenza virus H3N2 hemagglutinin
Maggie Haitian Wang[SUP] 1 [/SUP], Jingzhi Lou[SUP] 2 [/SUP], Lirong Cao[SUP] 2 [/SUP], Shi Zhao[SUP] 2 [/SUP], Renee Wy Chan[SUP] 3 [/SUP], Paul Ks Chan[SUP] 4 [/SUP], Martin Chi-Wai Chan[SUP] 4 [/SUP], Marc Kc Chong[SUP] 2 [/SUP], William Kk Wu[SUP] 5 [/SUP], Yuchen Wei[SUP] 4 [/SUP], Haoyang Zhang[SUP] 6 [/SUP], Benny Cy Zee[SUP] 2 [/SUP], Eng-Kiong Yeoh[SUP] 7 [/SUP]
Affiliations
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. 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 South-east 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.
Keywords: H3N2; Influenza virus genetics; Mutations; genetic epidemiology.
. 2021 Oct 7;S0163-4453(21)00498-9.
doi: 10.1016/j.jinf.2021.09.026. Online ahead of print.
Characterization of key amino acid substitutions and dynamics of the influenza virus H3N2 hemagglutinin
Maggie Haitian Wang[SUP] 1 [/SUP], Jingzhi Lou[SUP] 2 [/SUP], Lirong Cao[SUP] 2 [/SUP], Shi Zhao[SUP] 2 [/SUP], Renee Wy Chan[SUP] 3 [/SUP], Paul Ks Chan[SUP] 4 [/SUP], Martin Chi-Wai Chan[SUP] 4 [/SUP], Marc Kc Chong[SUP] 2 [/SUP], William Kk Wu[SUP] 5 [/SUP], Yuchen Wei[SUP] 4 [/SUP], Haoyang Zhang[SUP] 6 [/SUP], Benny Cy Zee[SUP] 2 [/SUP], Eng-Kiong Yeoh[SUP] 7 [/SUP]
Affiliations
- PMID: 34627840
- DOI: 10.1016/j.jinf.2021.09.026
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. 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 South-east 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.
Keywords: H3N2; Influenza virus genetics; Mutations; genetic epidemiology.