The Ongoing Epidemics of Seasonal Influenza A(H3N2) in Hangzhou, China, and Its Viral Genetic Diversity

This study examined the genetic and evolutionary features of influenza A/H3N2 viruses in Hangzhou (2010–2022) by analyzing 28,651 influenza-like illness samples from two sentinel hospitals. Influenza A/H3N2 coexisted with other subtypes, dominating seasonal peaks (notably summer). Whole-genome seque...

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Main Authors: Xueling Zheng, Feifei Cao, Yue Yu, Xinfen Yu, Yinyan Zhou, Shi Cheng, Xiaofeng Qiu, Lijiao Ao, Xuhui Yang, Zhou Sun, Jun Li
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/4/526
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author Xueling Zheng
Feifei Cao
Yue Yu
Xinfen Yu
Yinyan Zhou
Shi Cheng
Xiaofeng Qiu
Lijiao Ao
Xuhui Yang
Zhou Sun
Jun Li
author_facet Xueling Zheng
Feifei Cao
Yue Yu
Xinfen Yu
Yinyan Zhou
Shi Cheng
Xiaofeng Qiu
Lijiao Ao
Xuhui Yang
Zhou Sun
Jun Li
author_sort Xueling Zheng
collection DOAJ
description This study examined the genetic and evolutionary features of influenza A/H3N2 viruses in Hangzhou (2010–2022) by analyzing 28,651 influenza-like illness samples from two sentinel hospitals. Influenza A/H3N2 coexisted with other subtypes, dominating seasonal peaks (notably summer). Whole-genome sequencing of 367 strains was performed on GridION platforms. Phylogenetic analysis showed they fell into 16 genetic groups, with multiple clades circulating simultaneously. Shannon entropy indicated HA, NA, and NS gene segments exhibited significantly higher variability than other genomic segments, with HA glycoprotein mutations concentrated in antigenic epitopes A–E. Antiviral resistance showed no inhibitor resistance mutations in PA, PB1, or PB2, but NA mutations were detected in some strains, and most strains harbored M2 mutations. A Bayesian molecular clock showed the HA segment exhibited the highest nucleotide substitution rate (3.96 × 10<sup>−3</sup> substitutions/site/year), followed by NA (3.77 × 10<sup>−3</sup>) and NS (3.65 × 10<sup>−3</sup>). Selective pressure showed A/H3N2 strains were predominantly under purifying selection, with only sporadic positive selection at specific sites. The Pepitope model demonstrated that antigenic epitope mismatches between circulating H3N2 variants and vaccine strains led to a significant decline in influenza vaccine effectiveness (VE), particularly in 2022. Overall, the study underscores the complex circulation patterns of influenza in Hangzhou and the global importance of timely vaccine strain updates.
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spelling doaj-art-cdb007b6de714ee89de8a1fcd42a5aa52025-08-20T02:18:16ZengMDPI AGViruses1999-49152025-04-0117452610.3390/v17040526The Ongoing Epidemics of Seasonal Influenza A(H3N2) in Hangzhou, China, and Its Viral Genetic DiversityXueling Zheng0Feifei Cao1Yue Yu2Xinfen Yu3Yinyan Zhou4Shi Cheng5Xiaofeng Qiu6Lijiao Ao7Xuhui Yang8Zhou Sun9Jun Li10Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaHangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou 310002, ChinaThis study examined the genetic and evolutionary features of influenza A/H3N2 viruses in Hangzhou (2010–2022) by analyzing 28,651 influenza-like illness samples from two sentinel hospitals. Influenza A/H3N2 coexisted with other subtypes, dominating seasonal peaks (notably summer). Whole-genome sequencing of 367 strains was performed on GridION platforms. Phylogenetic analysis showed they fell into 16 genetic groups, with multiple clades circulating simultaneously. Shannon entropy indicated HA, NA, and NS gene segments exhibited significantly higher variability than other genomic segments, with HA glycoprotein mutations concentrated in antigenic epitopes A–E. Antiviral resistance showed no inhibitor resistance mutations in PA, PB1, or PB2, but NA mutations were detected in some strains, and most strains harbored M2 mutations. A Bayesian molecular clock showed the HA segment exhibited the highest nucleotide substitution rate (3.96 × 10<sup>−3</sup> substitutions/site/year), followed by NA (3.77 × 10<sup>−3</sup>) and NS (3.65 × 10<sup>−3</sup>). Selective pressure showed A/H3N2 strains were predominantly under purifying selection, with only sporadic positive selection at specific sites. The Pepitope model demonstrated that antigenic epitope mismatches between circulating H3N2 variants and vaccine strains led to a significant decline in influenza vaccine effectiveness (VE), particularly in 2022. Overall, the study underscores the complex circulation patterns of influenza in Hangzhou and the global importance of timely vaccine strain updates.https://www.mdpi.com/1999-4915/17/4/526influenza A/H3N2whole-genome sequencingphylogenetic analysisShannon entropyantiviral resistanceBayesian molecular clock
spellingShingle Xueling Zheng
Feifei Cao
Yue Yu
Xinfen Yu
Yinyan Zhou
Shi Cheng
Xiaofeng Qiu
Lijiao Ao
Xuhui Yang
Zhou Sun
Jun Li
The Ongoing Epidemics of Seasonal Influenza A(H3N2) in Hangzhou, China, and Its Viral Genetic Diversity
Viruses
influenza A/H3N2
whole-genome sequencing
phylogenetic analysis
Shannon entropy
antiviral resistance
Bayesian molecular clock
title The Ongoing Epidemics of Seasonal Influenza A(H3N2) in Hangzhou, China, and Its Viral Genetic Diversity
title_full The Ongoing Epidemics of Seasonal Influenza A(H3N2) in Hangzhou, China, and Its Viral Genetic Diversity
title_fullStr The Ongoing Epidemics of Seasonal Influenza A(H3N2) in Hangzhou, China, and Its Viral Genetic Diversity
title_full_unstemmed The Ongoing Epidemics of Seasonal Influenza A(H3N2) in Hangzhou, China, and Its Viral Genetic Diversity
title_short The Ongoing Epidemics of Seasonal Influenza A(H3N2) in Hangzhou, China, and Its Viral Genetic Diversity
title_sort ongoing epidemics of seasonal influenza a h3n2 in hangzhou china and its viral genetic diversity
topic influenza A/H3N2
whole-genome sequencing
phylogenetic analysis
Shannon entropy
antiviral resistance
Bayesian molecular clock
url https://www.mdpi.com/1999-4915/17/4/526
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