Epidemiological and genomic surveillance of influenza A virus (pdm09 H1N1 and H3N2) strains from 2017 to 2025 in Tianjin, China

Mingkun Wu; Liru Guo; Mei Kong; Ming Zou; Xiaochang Liu; Xiaoyan Li

doi:10.1016/j.virs.2025.07.011

August 2025

. doi: 10.1016/j.virs.2025.07.011

Citation: Mingkun Wu, Liru Guo, Mei Kong, Ming Zou, Xiaochang Liu, Xiaoyan Li. Epidemiological and genomic surveillance of influenza A virus (pdm09 H1N1 and H3N2) strains from 2017 to 2025 in Tianjin, China .VIROLOGICA SINICA, 2025, 40(4) : 535-545. http://dx.doi.org/10.1016/j.virs.2025.07.011

2017-2025年天津市甲型流感病毒株（pdm09 H1N1和H3N2）流行病学和基因组监测研究

吴明琨 ^a,b ,
郭丽茹 ^a,b ,
孔梅 ^a,b ,
邹明 ^a,b ,
刘小畅 ^a,b ,
李晓燕 ^a,b,c,,

a 天津市疾病预防控制中心微生物检验检测所;
b 天津市传染病病原微生物重点实验室;
c 天津医科大学人群重大疾病预防控制教育部重点实验室

通讯作者： 李晓燕, xiaoyanli1291@163.com
收稿日期： 2025-04-21
录用日期： 2025-07-25

摘要

甲型流感病毒（IAV）感染仍然是重要的全球公共卫生问题，可引起流感样症状和严重呼吸道感染。目前全球流行的IAV包括A/pdm09 H1N1和A/H3N2两种主要亚型，其流行受多种因素影响，在新冠疫情期间表现尤为显著。基于中国国家流感监测项目的数据，本研究分析了天津市2017-2025年甲型流感病毒的流行病学和基因组数据。研究期间共收集咽拭子样本77473份，其中9144份经检测呈IAV阳性。结果显示，A/pdm09 H1N1和A/H3N2谱系在不同的流感季节表现出不同的流行趋势，尤其是在新冠疫情期间，感染病例数呈现下降趋势。作者对128株A/pdm09 H1N1和113株A/H3N2临床分离株进行了全基因组测序，并基于时间尺度的系统发育分析对其动态进化和遗传多样性进行了深入研究。同时，作者针对甲型流感病毒血凝素和神经氨酸酶片段进行了基因组风险评估，确定了与病毒适应性、传播性、毒力和耐药性相关的关键氨基酸位点。此外，在近期流感流行季的临床分离株中，未发现抗原变异，但个别毒株对奥司他韦和扎那米韦的敏感性出现降低。综上，本研究通过系统监测，重点阐明了天津市2017-2025年甲型流感病毒的流行病学特征及演变规律，为流感防控提供了科学依据。
- 流行病学
- , 甲型流感病毒
- , 高通量测序
- , 抗原性
- , 耐药性

Epidemiological and genomic surveillance of influenza A virus (pdm09 H1N1 and H3N2) strains from 2017 to 2025 in Tianjin, China

Mingkun Wu ^a,b ,
Liru Guo ^a,b ,
Mei Kong ^a,b ,
Ming Zou ^a,b ,
Xiaochang Liu ^a,b ,
Xiaoyan Li ^a,b,c,,

a. Institute of Microbiology, Tianjin Centers for Disease Control and Prevention, Tianjin, 300011, China;
b. Tianjin Key Laboratory of Pathogenic Microbiology of Infectious Disease, Centers for Disease Control and Prevention, Tianjin, 300011, China;
c. Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin, 300070, China

Corresponding author: Xiaoyan Li, xiaoyanli1291@163.com
Received Date: 21 April 2025
Accepted Date: 25 July 2025

Abstract

Influenza A virus (IAV) remains a global public health concern, causing influenza-like illness and severe respiratory tract infections. Two major subtypes, A/pdm09 H1N1 and A/H3N2, circulate globally, and their epidemics are influenced by multiple factors, especially during the COVID-19 pandemic. Based on data from the National Influenza Surveillance Program in China, we analyzed the epidemiological and genomic data in Tianjin collected from 2017 to 2025. A total of 77,473 throat swabs were collected, of which 9144 were IAV-positive. The A/pdm09 H1N1 and A/H3N2 lineages exhibited distinct epidemics across different influenza seasons, with a decline in cases observed during the COVID-19 pandemic. We sequenced the genomes of 128 A/pdm09 H1N1 and 113 A/H3N2 clinical isolates and characterized their temporal evolution and genetic diversity using time-scaled phylogenetic analysis. Additionally, we conducted a genetic risk evaluation of the hemagglutinin and neuraminidase segments, identifying key amino acid residues associated with viral adaptation, transmissibility, virulence, and drug resistance. Moreover, no antigenic variants were found in clinical isolates during the recent influenza seasons, though reduced sensitivity to oseltamivir and zanamivir was observed in individual strains. Our surveillance highlights the epidemiology and evolution of IAV before and after the COVID-19 pandemic in Tianjin.
- Epidemiology
- , Influenza A virus (IAV)
- , Next-generation sequencing
- , Antigenicity
- , Drug resistance

References
1. Aksamentov, I., Roemer, C., Hodcroft, E.,Neher, R., 2021. Nextclade: clade assignment, mutation calling and quality control for viral genomes. Journal of Open Source Software, 6.
2. Altschul, S.F., Gish, W., Miller, W., Myers, E.W.,Lipman, D.J., 1990. Basic local alignment search tool. J Mol Biol, 215, 403-410.
3. An, S.H., Lee, C.Y., Hong, S.M., Song, C.S., Kim, J.H.,Kwon, H.J., 2019. Novel Mutations Evading Avian Immunity around the Receptor Binding Site of the Clade 2.3.2.1c Hemagglutinin Gene Reduce Viral Thermostability and Mammalian Pathogenicity. Viruses, 11.
4. Andreev, K., Jones, J.C., Seiler, P., Kandeil, A., Webby, R.J.,Govorkova, E.A., 2024. Genotypic and phenotypic susceptibility of emerging avian influenza A viruses to neuraminidase and cap-dependent endonuclease inhibitors. Antiviral Res, 229, 105959.
5. Bai, L., Zhao, Y., Dong, J., Liang, S., Guo, M., Liu, X., Wang, X., Huang, Z., Sun, X., Zhang, Z., et al., 2021. Coinfection with influenza A virus enhances SARS-CoV-2 infectivity. Cell Res, 31, 395-403.
6. Behera, A.K., Chandra, I.,Cherian, S.S., 2016. Molecular dynamics simulation of the effects of single (S221P) and double (S221P and K216E) mutations in the hemagglutinin protein of influenza A H5N1 virus: a study on host receptor specificity. J Biomol Struct Dyn, 34, 2054-2067.
7. Boivin, G., 2013. Detection and management of antiviral resistance for influenza viruses. Influenza Other Respir Viruses, 7 Suppl 3, 18-23.
8. Boltz, D.A., Douangngeun, B., Phommachanh, P., Sinthasak, S., Mondry, R., Obert, C., Seiler, P., Keating, R., Suzuki, Y., Hiramatsu, H., Govorkova, E.A.,Webster, R.G., 2010. Emergence of H5N1 avian influenza viruses with reduced sensitivity to neuraminidase inhibitors and novel reassortants in Lao People's Democratic Republic. J Gen Virol, 91, 949-959.
9. Butler, J., Hooper, K.A., Petrie, S., Lee, R., Maurer-Stroh, S., Reh, L., Guarnaccia, T., Baas, C., Xue, L., Vitesnik, S., Leang, S.K., Mcvernon, J., Kelso, A., Barr, I.G., Mccaw, J.M., Bloom, J.D.,Hurt, A.C., 2014. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses. PLoS Pathog, 10, e1004065.
10. Chandrasekaran, A., Srinivasan, A., Raman, R., Viswanathan, K., Raguram, S., Tumpey, T.M., Sasisekharan, V.,Sasisekharan, R., 2008. Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin. Nat Biotechnol, 26, 107-113.
11. Chen, Z., Tsui, J.L., Gutierrez, B., Busch Moreno, S., Du Plessis, L., Deng, X., Cai, J., Bajaj, S., Suchard, M.A., Pybus, O.G., Lemey, P., Kraemer, M.U.G.,Yu, H., 2024. COVID-19 pandemic interventions reshaped the global dispersal of seasonal influenza viruses. Science, 386, eadq3003.
12. Chon, I., Win, S.M.K., Phyu, W.W., Saito, R., Kyaw, Y., Win, N.C., Lasham, D.J., Tin, H.H., Tamura, T., Otoguro, T., Wagatsuma, K., Sun, Y., Li, J.,Watanabe, H., 2024. Whole-Genome Analysis of the Influenza A(H1N1)pdm09 Viruses Isolated from Influenza-like Illness Outpatients in Myanmar and Community-Acquired Oseltamivir-Resistant Strains Present from 2015 to 2019. Viruses, 16.
13. Conroy, G., 2023. What's behind China's mysterious wave of childhood pneumonia? Nature, 10.1038/d41586-023-03732-w.
14. De Vries, R.P., Tzarum, N., Peng, W., Thompson, A.J., Ambepitiya Wickramasinghe, I.N., De La Pena, A.T.T., Van Breemen, M.J., Bouwman, K.M., Zhu, X., Mcbride, R., Yu, W., Sanders, R.W., Verheije, M.H., Wilson, I.A.,Paulson, J.C., 2017. A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors. EMBO Mol Med, 9, 1314-1325.
15. Dhanasekaran, V., Sullivan, S., Edwards, K.M., Xie, R., Khvorov, A., Valkenburg, S.A., Cowling, B.J.,Barr, I.G., 2022. Human seasonal influenza under COVID-19 and the potential consequences of influenza lineage elimination. Nat Commun, 13, 1721.
16. Fahim, M., Roshdy, W.H., Deghedy, O., Kamel, R., Naguib, A., Showky, S., Elguindy, N., Abdel Fattah, M., Afifi, S., Mohsen, A., Kandeel, A.,Abdelghaffar, K., 2022. Epidemiology, Disease Severity and Outcome of Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza Viruses Coinfection Seen at Egypt Integrated Acute Respiratory Infections Surveillance, 2020-2022. Can J Infect Dis Med Microbiol, 2022, 7497500.
17. Gamblin, S.J.,Skehel, J.J., 2010. Influenza hemagglutinin and neuraminidase membrane glycoproteins. J Biol Chem, 285, 28403-28409.
18. Garten, R.J., Davis, C.T., Russell, C.A., Shu, B., Lindstrom, S., Balish, A., Sessions, W.M., Xu, X., Skepner, E., Deyde, V., et al., 2009. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science, 325, 197-201.
19. Huang, Y., Li, S., Ye, W., Wang, H., Su, J., Gao, L., Shi, R., Mou, X., Leng, S.X., Xiao, C.,Chen, G., 2025. Viral Infections in Elderly Individuals: A Comprehensive Overview of SARS-CoV-2 and Influenza Susceptibility, Pathogenesis, and Clinical Treatment Strategies. Vaccines (Basel), 13.
20. Huo, X., Fu, J., Dai, Q.,Zhu, F., 2022. Influenza virus subtype/lineage-specific seasonal patterns and age-related infection risk, in Eastern China. J Infect Dev Ctries, 16, 1928-1932.
21. Hurt, A.C., Hardie, K., Wilson, N.J., Deng, Y.M., Osbourn, M., Gehrig, N.,Kelso, A., 2011. Community transmission of oseltamivir-resistant A(H1N1)pdm09 influenza. N Engl J Med, 365, 2541-2542.
22. Imai, M., Watanabe, T., Hatta, M., Das, S.C., Ozawa, M., Shinya, K., Zhong, G., Hanson, A., Katsura, H., Watanabe, S., Li, C., Kawakami, E., Yamada, S., Kiso, M., Suzuki, Y., Maher, E.A., Neumann, G.,Kawaoka, Y., 2012. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature, 486, 420-428.
23. Jayaraman, A., Pappas, C., Raman, R., Belser, J.A., Viswanathan, K., Shriver, Z., Tumpey, T.M.,Sasisekharan, R., 2011. A single base-pair change in 2009 H1N1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets. PLoS One, 6, e17616.
24. Kawai, N., Ikematsu, H., Iwaki, N., Kondou, K., Hirotsu, N., Kawashima, T., Maeda, T., Tanaka, O., Doniwa, K.,Kashiwagi, S., 2009. Clinical effectiveness of oseltamivir for influenza A(H1N1) virus with H274Y neuraminidase mutation. J Infect, 59, 207-212.
25. Khare, S., Gurry, C., Freitas, L., Schultz, M.B., Bach, G., Diallo, A., Akite, N., Ho, J., Lee, R.T., Yeo, W., Curation Team, G.C.,Maurer-Stroh, S., 2021. GISAID's Role in Pandemic Response. China CDC Wkly, 3, 1049-1051.
26. Kim, E.H., Nguyen, T.Q., Casel, M.a.B., Rollon, R., Kim, S.M., Kim, Y.I., Yu, K.M., Jang, S.G., Yang, J., Poo, H., Jung, J.U.,Choi, Y.K., 2022. Coinfection with SARS-CoV-2 and Influenza A Virus Increases Disease Severity and Impairs Neutralizing Antibody and CD4(+) T Cell Responses. J Virol, 96, e0187321.
27. Krammer, F., Smith, G.J.D., Fouchier, R.a.M., Peiris, M., Kedzierska, K., Doherty, P.C., Palese, P., Shaw, M.L., Treanor, J., Webster, R.G.,Garcia-Sastre, A., 2018. Influenza. Nat Rev Dis Primers, 4, 3.
28. Lackenby, A., Moran Gilad, J., Pebody, R., Miah, S., Calatayud, L., Bolotin, S., Vipond, I., Muir, P., Guiver, M., Mcmenamin, J., Reynolds, A., Moore, C., Gunson, R., Thompson, C., Galiano, M., Bermingham, A., Ellis, J.,Zambon, M., 2011. Continued emergence and changing epidemiology of oseltamivir-resistant influenza A(H1N1)2009 virus, United Kingdom, winter 2010/11. Euro Surveill, 16.
29. Lee, A.J., Carson, S., Reyne, M.I., Marshall, A., Moody, D., Allen, D.M., Allingham, P., Levickas, A., Fitzgerald, A., Bell, S.H., et al., 2024. Wastewater monitoring of human and avian influenza A viruses in Northern Ireland: a genomic surveillance study. Lancet Microbe, 10.1016/s2666-5247(24)00175-7, 100933.
30. Lee, N., Khalenkov, A.M., Lugovtsev, V.Y., Ireland, D.D., Samsonova, A.P., Bovin, N.V., Donnelly, R.P.,Ilyushina, N.A., 2018. The use of plant lectins to regulate H1N1 influenza A virus receptor binding activity. PLoS One, 13, e0195525.
31. Li, X., Dong, Z., Li, J., Dou, C., Tian, D., Ma, Z., Liu, W., Gao, G. F., Bi, Y., 2024. Genetic characteristics of H1N1 influenza virus outbreak in China in early 2023. Virol Sin. 39, 520–523.
32. Mo, J.S., Abente, E.J., Cardenas Perez, M., Sutton, T.C., Cowan, B., Ferreri, L.M., Geiger, G., Gauger, P.C., Perez, D.R., Vincent Baker, A.L.,Rajao, D.S., 2022. Transmission of Human Influenza A Virus in Pigs Selects for Adaptive Mutations on the HA Gene. J Virol, 96, e0148022.
33. Nair, H., Brooks, W.A., Katz, M., Roca, A., Berkley, J.A., Madhi, S.A., Simmerman, J.M., Gordon, A., Sato, M., Howie, S., et al., 2011. Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet, 378, 1917-1930.
34. Nelson, M.I., Viboud, C., Simonsen, L., Bennett, R.T., Griesemer, S.B., St George, K., Taylor, J., Spiro, D.J., Sengamalay, N.A., Ghedin, E., Taubenberger, J.K.,Holmes, E.C., 2008. Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918. PLoS Pathog, 4, e1000012.
35. Olsen, S.J., Azziz-Baumgartner, E., Budd, A.P., Brammer, L., Sullivan, S., Pineda, R.F., Cohen, C.,Fry, A.M., 2020. Decreased Influenza Activity During the COVID-19 Pandemic - United States, Australia, Chile, and South Africa, 2020. MMWR Morb Mortal Wkly Rep, 69, 1305-1309.
36. Peng, Y., Wang, D., Wang, J., Li, K., Tan, Z., Shu, Y.,Jiang, T., 2017. A universal computational model for predicting antigenic variants of influenza A virus based on conserved antigenic structures. Sci Rep, 7, 42051.
37. Suchard, M.A., Lemey, P., Baele, G., Ayres, D.L., Drummond, A.J.,Rambaut, A., 2018. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus Evol, 4, vey016.
38. Takashita, E., Kiso, M., Fujisaki, S., Yokoyama, M., Nakamura, K., Shirakura, M., Sato, H., Odagiri, T., Kawaoka, Y.,Tashiro, M., 2015. Characterization of a large cluster of influenza A(H1N1)pdm09 viruses cross-resistant to oseltamivir and peramivir during the 2013-2014 influenza season in Japan. Antimicrob Agents Chemother, 59, 2607-2617.
39. Tang, C.Y., Boftsi, M., Staudt, L., Mcelroy, J.A., Li, T., Duong, S., Ohler, A., Ritter, D., Hammer, R., Hang, J.,Wan, X.F., 2022. SARS-CoV-2 and influenza co-infection: A cross-sectional study in central Missouri during the 2021-2022 influenza season. Virology, 576, 105-110.
40. Tsou, T.P., Su, C.P., Huang, W.T., Yang, J.R.,Liu, M.T., 2017. Influenza A(H3N2) virus variants and patient characteristics during a summer influenza epidemic in Taiwan, 2017. Euro Surveill, 22.
41. Wagner, R., Matrosovich, M.,Klenk, H.D., 2002. Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol, 12, 159-166.
42. Wang, W., Lu, B., Zhou, H., Suguitan, A.L., Jr., Cheng, X., Subbarao, K., Kemble, G.,Jin, H., 2010. Glycosylation at 158N of the hemagglutinin protein and receptor binding specificity synergistically affect the antigenicity and immunogenicity of a live attenuated H5N1 A/Vietnam/1203/2004 vaccine virus in ferrets. J Virol, 84, 6570-6577.
43. Wedde, M., Biere, B., Wolff, T.,Schweiger, B., 2015. Evolution of the hemagglutinin expressed by human influenza A(H1N1)pdm09 and A(H3N2) viruses circulating between 2008-2009 and 2013-2014 in Germany. Int J Med Microbiol, 305, 762-775.
44. Xing, L., Chen, Y., Chen, B., Bu, L., Liu, Y., Zeng, Z., Guan, W., Chen, Q., Lin, Y., Qin, K., Chen, H., Deng, X., Wang, X.,Song, W., 2021. Antigenic Drift of the Hemagglutinin from an Influenza A (H1N1) pdm09 Clinical Isolate Increases its Pathogenicity In Vitro. Virol Sin, 36, 1220-1227.
45. Ye, J., Sorrell, E.M., Cai, Y., Shao, H., Xu, K., Pena, L., Hickman, D., Song, H., Angel, M., Medina, R.A., Manicassamy, B., Garcia-Sastre, A.,Perez, D.R., 2010. Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype? PLoS Pathog, 6, e1001145.
46. Zhao, X., Gu, Y., Tang, X., Jiang, C., Fang, F., Chu, W., Tao, L., Zhang, X., Chen, M., Wu, H., Xie, Y., Liu, J.,Teng, Z., 2024. Whole-genome analysis of circulating influenza A virus (H3N2) strains in Shanghai, China from 2005 to 2023. Emerg Microbes Infect, 13, 2396867.
Proportional views

Electronic Supplementary Material

10.1016j.virs.2025.07.011-ESM-ESM8.xlsx
10.1016j.virs.2025.07.011-ESM-ESM4.xlsx
10.1016j.virs.2025.07.011-ESM-ESM2.xlsx
10.1016j.virs.2025.07.011-ESM-ESM7.xlsx
10.1016j.virs.2025.07.011-ESM-ESM9.xlsx
10.1016j.virs.2025.07.011-ESM-ESM1.docx
10.1016j.virs.2025.07.011-ESM-ESM3.xlsx
10.1016j.virs.2025.07.011-ESM-ESM6.xlsx
10.1016j.virs.2025.07.011-ESM-ESM5.xlsx