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Volume 36 Issue 5
October 2021
    Citation: Lei Xing, Yunbo Chen, Boqian Chen, Ling Bu, Ying Liu, Zhiqi Zeng, Wenda Guan, Qigao Chen, Yongping Lin, Kun Qin, Honglin Chen, Xilong Deng, Xinhua Wang, Wenjun Song. Antigenic Drift of the Hemagglutinin from an Influenza A (H1N1) pdm09 Clinical Isolate Increases its Pathogenicity In Vitro .VIROLOGICA SINICA, 2021, 36(5) : 1220-1227.  http://dx.doi.org/10.1007/s12250-021-00401-y
    shu

    Antigenic Drift of the Hemagglutinin from an Influenza A (H1N1) pdm09 Clinical Isolate Increases its Pathogenicity In Vitro

    • 1.

      State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China

    • 2.

      Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

    • 3.

      Institute of Integration of Traditional and Western Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China

    • 4.

      Intensive Care Unit, Guangzhou No.8 People's Hospital of Guangzhou Medical University, Guangzhou 510060, China

    • 5.

      State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China

    • 6.

      China CDC, National Institute for Viral Disease Control and Prevention, Beijing 100052, China

    • Corresponding author: Honglin Chen, hlchen@hku.hk, ORCID: http://orcid.org/0000-0001-5108-8338
      Xilong Deng, xlodeng@126.com, ORCID: http://orcid.org/0000-0002-1085-5155
      Xinhua Wang, xinhuaw@gzhmu.edu.cn, ORCID: http://orcid.org/0000-0001-9118-3719
      Wenjun Song, wjsong@hku.hk, ORCID: http://orcid.org/0000-0002-0165-7894
    • Lei Xing and Yunbo Chen have contributed equally to this work.
    • Received Date: 06 January 2021
      Accepted Date: 12 April 2021
      Published Date: 09 June 2021
      Available online: 01 October 2021

    • The influenza A (H1N1) pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years. Here, we analyzed a clinical influenza A (H1N1) pdm09-infected patient case hospitalized for two months in Guangdong (from December 14, 2019 to February 15, 2020). This isolate, named A/Guangdong/LCF/2019 (LCF/19), was genetically sequenced, rescued by reverse genetics, and phylogenetically analyzed in the context of other relevant pdm09 isolates. Compared with earlier isolates, this pdm09 virus's genetic sequence contains four substitutions, S186P, T188I, D190A, and Q192E, of the hemagglutinin (HA) segment at position 186–192 (H3 numbering) in the epitope Sb, and two of which are located at the 190-helix. Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in 2018. To characterize the pathogenicity of this novel substitution motif, a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued. Kinetic growth data revealed that the reassortant viruses, including the LCF/2019 with the PTIAAQE substitution, propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney (MDCK) cells. The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018, suggesting that old vaccines might not effectively protect people from infection. Due to the difference in the selection of vaccine strains, people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.

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      Antigenic Drift of the Hemagglutinin from an Influenza A (H1N1) pdm09 Clinical Isolate Increases its Pathogenicity In Vitro

        Corresponding author: Honglin Chen, hlchen@hku.hk
        Corresponding author: Xilong Deng, xlodeng@126.com
        Corresponding author: Xinhua Wang, xinhuaw@gzhmu.edu.cn
        Corresponding author: Wenjun Song, wjsong@hku.hk
      • 1. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
      • 2. Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
      • 3. Institute of Integration of Traditional and Western Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510180, China
      • 4. Intensive Care Unit, Guangzhou No.8 People's Hospital of Guangzhou Medical University, Guangzhou 510060, China
      • 5. State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China
      • 6. China CDC, National Institute for Viral Disease Control and Prevention, Beijing 100052, China
      • Received Date: 06 January 2021
      • Accepted Date: 12 April 2021
      • Published Date: 09 June 2021

      Abstract: 

      The influenza A (H1N1) pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years. Here, we analyzed a clinical influenza A (H1N1) pdm09-infected patient case hospitalized for two months in Guangdong (from December 14, 2019 to February 15, 2020). This isolate, named A/Guangdong/LCF/2019 (LCF/19), was genetically sequenced, rescued by reverse genetics, and phylogenetically analyzed in the context of other relevant pdm09 isolates. Compared with earlier isolates, this pdm09 virus's genetic sequence contains four substitutions, S186P, T188I, D190A, and Q192E, of the hemagglutinin (HA) segment at position 186–192 (H3 numbering) in the epitope Sb, and two of which are located at the 190-helix. Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in 2018. To characterize the pathogenicity of this novel substitution motif, a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued. Kinetic growth data revealed that the reassortant viruses, including the LCF/2019 with the PTIAAQE substitution, propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney (MDCK) cells. The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018, suggesting that old vaccines might not effectively protect people from infection. Due to the difference in the selection of vaccine strains, people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.

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