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The genetic characterization of hemagglutinin (HA), neuraminidase (NA) and polymerase acidic (PA) genes of H3N2 influenza viruses circulated in Guangdong Province of China during 2019–2020


The evolution of seasonal influenza viruses, which can cause virus antigenic drift to escape human herd immunity, is a significant public health problem. Here, we obtained hemagglutinin (HA), neuraminidase (NA), and polymerase acidic protein (PA) the gene sequences of 84 influenza virus isolates collected in Guangdong Province during the 2019–2020 influenza season. Phylogenetic analyses revealed all these isolates were genetically similar to the viruses of clade 3C2a A1b, specifically those within subclades of A1b 137F (59 cases), A1b 186D (19 cases), and A1b 94 N (6 cases). The influenza virus isolates were distinct from the World Health Organization recommended influenza A vaccine virus for the 2019–2020 Northern Hemisphere season (A/Kansas/14/2017; H3N2). Phylogenies inferred from the individual gene segment sequences revealed that one reassortment event occurred among these clades. The genetic variation involved mutations within viral antigenic epitopes and two n-glycosylation site alterations. The novel mutation sites of G202D and D206N in the HA gene, E344K in the NA gene, and K626R in the PA gene which may affect the spread of the virus were observed. We investigated the evolution of these genes and found that the HA and NA genes were under greater pressure than PA gene. Mutations associated with conferring resistance to NA inhibitors or baloxavir acid were not found. Our results suggest that a rapid evolution of the H3N2 influenza virus occurred, thus continuous monitoring is critical for establishing appropriate vaccine formulations or drug delivery for targeting influenza.

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The raw data used in this study are available from the corresponding author upon reasonable request.

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Polymerase acidic


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We thank the laboratory staff Wei Zhang in the diagnostic and research laboratory for respiratory virus in Guangzhou KingMed Diagnostics. We also thank professor Jingxian Chen for revising the manuscript.


This work was supported by the National Key Research and Development Program of China (Grant No. 2020YFA0708002), Zhongnanshan Medical Foundation of Guangdong Province (Grant No. ZNSA-2020012), Science and Technology Program of Foshan (Grant No. 2020001000206), Science and Technology Program of Guangzhou (Grant No. 202102100003), China Evergrande Group-2020GIRHHMS23, 2020GIRHHMS01, 2020GIRHHMS18, National Natural Science Foundation of Guangdong (Grant No. 2020B1515120045), National Natural Science Foundation of Guizhou (Grant No. [2020] 4Y219), Science and Technology Bureau Project of Dongguan (Grant No. 202071715001114).

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Authors and Affiliations



YL, WJ and ZY: contributed to study conception and design. WJ: contributed to data collection and analysis. WJ: contributed to drafting and editing the manuscript. YL: revised the manuscript. ZY: provided study supervision. All authors read and approved the final manuscript.

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Correspondence to Zifeng Yang.

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This study was approved by the ethics committee of KingMed Diagnostics.

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Liu, Y., Jin, W., Guan, W. et al. The genetic characterization of hemagglutinin (HA), neuraminidase (NA) and polymerase acidic (PA) genes of H3N2 influenza viruses circulated in Guangdong Province of China during 2019–2020. Virus Genes 58, 392–402 (2022).

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  • H3N2
  • phylogeny
  • Mutation
  • Antigenic drift
  • Resistance