Effect of Mutations in Hemagglutinin and Neurominidase on the Properties of Seasonal Influenza Viruses

Authors

  • V.I. Zadorozhna SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine», 5 Amosova Str., Kyiv, 03038, Ukraine https://orcid.org/0000-0002-0917-2007
  • M.G. Liulchuk SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine», 5 Amosova Str., Kyiv, 03038, Ukraine https://orcid.org/0000-0001-7689-4002
  • V.R. Shahinian SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine», 5 Amosova Str., Kyiv, 03038, Ukraine https://orcid.org/0000-0002-2746-3414
  • T.A. Serheieva SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine», 5 Amosova Str., Kyiv, 03038, Ukraine https://orcid.org/0000-0001-6488-4042
  • N.P. Vynnyk SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine», 5 Amosova Str., Kyiv, 03038, Ukraine https://orcid.org/0000-0002-5608-005X
  • N.O. Vynograd SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine», 5 Amosova Str., Kyiv, 03038, Ukraine https://orcid.org/0000-0001-6133-6841
  • I.L. Marychev SI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases, National Academy of Medical Sciences of Ukraine», 5 Amosova Str., Kyiv, 03038, Ukraine https://orcid.org/0009-0008-0845-8493

DOI:

https://doi.org/10.15407/microbiolj88.01.104

Keywords:

influenza A(H1N1)pdm09 virus, influenza A(H3N2) virus, influenza B/Victoria virus, hemagglutinin, neuraminidase, mutation

Abstract

Seasonal influenza viruses are pathogens that pose a constant threat to human health. They circulate everywhere and cause seasonal rises in the incidence of varying degrees of intensity in the Northern and Southern Hemispheres. These viruses are characterized by variability both due to antigenic drift and connection with the ability to reassort genes. It is known that certain amino acid substitutions in the hemagglutinin (HA) of the virus contributed to its transition to the use of human cellular receptors, which caused pandemics. The aim of the work was to analyze the literature data on the possible impact of mutations in HA and neuraminidase (NA) of seasonal influenza viruses (A(H1N1)pdm09, A(H3N2), B/Victoria)) on their properties, epidemic potential, and degree of clinical manifestation of the disease. The B/Yamagata influenza virus has not been analyzed because its circulation has effectively stopped amid the COVID-19 pandemic. It has been shown that influenza viruses A(H1N1)pdm09, A(H3N2), and B/Victoria differ significantly in terms of evolution. In dynamics, it was demonstrated the amino acid substitutions that occurred in the HA and NA of influenza viruses, including those that affected antigenic properties, resistance of viruses to specific drugs, and clinical symptoms of influenza. Those mutations that contribute to the increase in the reproduction of viruses in cell cultures and chicken embryos and affect certain biological properties of the virus are also considered. Data on the comparison of mutations in influenza viruses of different clades and viruses circulating in different geographical areas are presented. It is shown that under virtually the same initial conditions, the A(H3N2) virus among other influenza viruses showed significantly higher epidemic activity against the background of the pandemic. In the future, as was observed before, the intensity of its circulation will decrease, and the prevalence of other influenza viruses will increase, to which a layer of susceptible population will accumulate over the time. During the pandemic, the circulation of B/Victoria viruses was significantly lower than that of A viruses, especially during the first pandemic seasons. B/Victoria viruses are characterized by less pronounced HA variability than influenza A viruses. The higher antigenic stability of the virus contributes to the longer circulation of certain genetic variants of the virus with a relatively stable level of intensity and the longer use of the same vaccine variants of the viruses. Despite the large amount of data on monitoring the evolution of seasonal influenza viruses and studying the impact of amino acid mutations in HA and NA on the biological properties of the virus, their epidemic potential, and virulence potential, there are still many issues that need to be studied.

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References

Abed, Y., Bouhy, X., L'Huillier A. G., Rhéaume, C., Pizzorno, A., Retamal, M., Fage, C., Dubé, K., Joly, M. H., Beaulieu, E., Mallett, C., Kaiser, L., & Boivin, G. (2016). The E119D neuraminidase mutation identified in a multidrug-resistant influenza A(H1N1)pdm09 isolate severely alters viral fitness in vitro and in animal models. Antiviral Res, 6-12. https://doi.org/10.1016/j.antiviral.2016.05.006

Allen, J. D., & Ross, T. M. (2018). H3N2 influenza viruses in humans: Viral mechanisms, evolution, and evaluation. Hum Vaccin Immunother, 14(8), 1840-1847. https://doi.org/10.1080/21645515.2018.1462639

Ayora-Talavera, G., Cetina-Montejo, L., Matos-Patrón, A., & Romero-Beltrán, L. (2014). Hemagglutinin variants of influenza A(H1N1)pdm09 virus with reduced affinity for sialic acid receptors. Arch Virol, 159(5), 1207-11. https://doi.org/10.1007/s00705-013-1934-x

Belser, J. A., Jayaraman, A., Raman, R., Pappas, C., Zeng, H., Cox, N. J., Katz, J. M., Terrence, R. S., & Tumpey, M. (2011). Effect of D222G mutation in the hemagglutinin protein on receptor binding, pathogenesis and transmissibility of the 2009 pandemic H1N1 influenza virus. PLoS One, 6, e25091. https://doi.org/10.1371/journal.pone.0025091

Benton, D. J., Gamblin, S. J., Rosenthal, P. B., & Skehel, J. J. (2020). Structural transitions in influenza haemagglutinin at membrane fusion pH. Nature, 583 (7814), 150-153. https://doi.org/10.1038/s41586-020-2333-6

Burke, D. F., & Smith, D. J. (2014). A recommended numbering scheme for influenza A HA subtypes. PLoS One, 9(11), e112302. https://doi.org/10.1371/journal.pone.0112302

Castelán-Vega, J. A., Magaña-Hernández, A., Jiménez-Alberto, A., & Ribas-Aparicio R, M. (2014). The hemagglutinin of the influenza A(H1N1)pdm09 is mutating towards stability. Adv Appl Bioinform Chem, 3(7), 37-44. https://doi.org/10.2147/AABC.S68934

Chambers, B. S., Li, Y., Hodinka, R. L., & Hensley, S. E. (2014). Recent H3N2 influenza virus clinical isolates rapidly acquire hemagglutinin or neuraminidase mutations when propagated for antigenic analyses. J Virol, 88(18), 10986-9. https://doi.org/10.1128/JVI.01077-14

Chan, P. K., Lee, N., Joynt, G. M., Choi, K. W., Cheung, J. L., Yeung, A. C., Lam, Ph.…. Hui, D. S. C. (2011). Clinical and virological course of infection with haemagglutinin D222G mutant strain of 2009 pandemic influenza A (H1N1) virus. J Clin Virol, 50(4), 320-4. https://doi.org/10.1016/j.jcv.2011.01.013

Chen, H., Zhou, X., Zheng, J., & Kwoh, C. K. (2016). Rules of co-occurring mutations characterize the antigenic evolution of human influenza A/H3N2, A/H1N1 and B viruses. BMC Med Genomics, 9(3), 69. https://doi.org/10.1186/s12920-016-0230-5

Chlanda, P., Mekhedov, E., Waters, H., Sodt, A., Schwartz, C., Nair, V., Blank, P. S., & Zimmerberg, J. (2017). Palmitoylation Contributes to Membrane Curvature in Influenza A Virus Assembly and Hemagglutinin-Mediated Membrane Fusion. J. Virol, 91, e00947-17. https://doi.org/10.1128/JVI.00947-17

Chong, Y., & Ikematsu, H. (2018). Spread of predominant neuraminidase and hemagglutinin co-mutations in the influenza A/H3N2 virus genome. J Infect Chemother, 24(3),193-8. https://doi.org/10.1016/j.jiac.2017.10.010

Colman, P. M. (1989). NA enzyme and antigen. In: Sasaki Y, editor. The influenza viruses. New York: Plenum Publishing Corporation, 175-218. https://doi.org/10.1007/978-1-4613-0811-9_4

European Centre for Disease Prevention and Control. Seasonal influenza 2021-2022. In: ECDC. Annual epidemiological report for 2021. Stockholm: ECDC; 2022. - https://www.ecdc.europa.eu/sites/default/files/documents/seasonal-influenza-annual-epidemiological-report-2020-2021.pdf

European Centre for Disease Prevention and Control. Seasonal influenza 2022−2023. In: ECDC. Annual Epidemiological Report for 2023. Stockholm: ECDC; 2023. - https://www.ecdc.europa.eu/sites/default/files/documents/seasonal-influenza-annual-epidemiological-report-2022-2023.pdf

Fall, A., Han, L., Yunker, M., Gong, Y. N., Li, T. J., Norton, J. M., Abdullah, O., Rothman, R. E., Fenstermacher, K. Z. J., Morris, C. P., Pekosz, A., Klein, E., & Mostafa, H. H. (2023). Evolution of Influenza A(H3N2) Viruses in 2 Consecutive Seasons of Genomic Surveillance, 2021-2023. Open Forum Infect Dis, 16, 10(12), ofad577. https://doi.org/10.1093/ofid/ofad577

Garjani, A., Chegini, A. M., Salehi, M., Tabibzadeh, A., Yousefi, P., Razizadeh, M. H., Esghaei, M., Esghaei, M., & Rohban, M. H. (2023). Forecasting influenza hemagglutinin mutations through the lens of anomaly detection. Sci Rep, 13(1), 14944. https://doi.org/10.1038/s41598-023-42089-y

Ghafoori, S. M., Petersen, G. F., Conrady, D. G., Calhoun, B. M., Stigliano, M. Z. Z., Baydo, R. O., Grice, R., Abendroth, J., Lorimer, D. D., Edwards, T. E., & Jade, K. (2023). Structural characterisation of hemagglutinin from seven Influenza A H1N1 strains reveal diversity in the C05 antibody recognition site. Sci Rep, 13, 6940. https://doi.org/10.1038/s41598-023-33529-w

Glaser, L., Stevens, J., Zamarin, D., Wilson, I. A., García-Sastre, A., Tumpey, T. M., Basler, C. F., Taubenberger, J. K., & Palese, P. (2005). A single amino acid substitution in 1918 influenza virus hemagglutinin changes receptor binding specificity. J Virol, 79(17), 11533-6. https://doi.org/10.1128/JVI.79.17.11533-11536.2005

Guldemir, D., Kalaycioglu, A. T., Altas, A. B., Korukluoglu, G., & Durmaz, R. (2013). Monitoring genetic diversity of influenza A(H1N1)pdm09 virus circulating during the post-pandemic period in Turkey. Jpn J Infect Dis, 66(4), 299-305. https://doi.org/10.7883/yoken.66.299

Harvala, H., Frampton, D., Grant, P., Raffle, J., & Nastouli, E. (2017). Emergence of a novel subclade of influenza A(H3N2) virus in London, December 2016 to January 2017. Eur Commun Dis Bull, 22, 30466. https://doi.org/10.2807/1560-7917.ES.2017.22.8.30466

Harvala, H., Frampton, D., Grant, P., Raffle, J., Ferns, R. B., Kozlakidis, Z., Kellam, P., Pillay, D., Hayward, A., & Nastouli, E. (2017). Emergence of a novel subclade of influenza A (H3N2) virus in London, December 2016 to January 2017. Eurosurveillance, 22(8), 30466. https://doi.org/10.2807/1560-7917.ES.2017.22.8.30466

Hay, A. J., Gregory, V., Douglas, A. R., & Lin, Y. P. (2001). The evolution of human influenza viruses. Philos Trans R Soc Lond B Biol Sci, 29, 356(1416), 1861-70. https://doi.org/10.1098/rstb.2001.0999

Hellferscee, O., Treurnicht, F., Gaelejwe, L., Moerdyk, A., Reubenson, G., McMorrow, M., Tempia, S., McAnerney, J., Walaza, S., Wolter, N., von Gottberg, A., & Cohen, C. (2021). Detection of Victoria lineage influenza B viruses with K162 and N163 deletions in the hemagglutinin gene, South Africa, 2018. Health Sci Rep, 17, 4(3), e367. https://doi.org/10.1002/hsr2.367

Hu, M., Kackos, C., Banoth, B., Ojha, C. R., Jones, J. C., Lei, S., Li, L., Kercher, L., Webby, R. J., & Russell, C. J. (2023). Hemagglutinin destabilization in H3N2 vaccine reference viruses skews antigenicity and prevents airborne transmission in ferrets. Sci Adv, 29, 9(13), eadf5182. https://doi.org/10.1126/sciadv.adf5182

Igarashi, M., Ito, K., Yoshida, R., Tomabechi, D., Kida, H., & Takada, A. (2010). Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin. PLoS ONE, 5, e8553. https://doi.org/10.1371/journal.pone.0008553

Ilyushina, N. A., Komatsu, T. E., Ince, W. L., Donaldson, E. F., Lee, N. O'Rear, J. J., & Raymond, P. D. (2019). Influenza A virus hemagglutinin mutations associated with use of neuraminidase inhibitors correlate with decreased inhibition by anti-influenza antibodies. Virol J, 16, 149. https://doi.org/10.1186/s12985-019-1258-x

International Committee on Taxonomy of Viruses. Taxon Details. History of the taxon: Species: Alphainfluenzavirus influenzae (2022 Release, MSL #38), https://ictv.global/taxonomy/taxondetails?taxnode_id=202203956&taxon_name=Alphainfluenzavirus%20influenzae

Kong, H., Fan, S., Takada, K., Imai, M., Neumann, G., & Kawaoka, Y. (2021). H3N2 Influenza Viruses with 12- or 16-Amino Acid Deletions in the Receptor-Binding Region of Their Hemagglutinin Protein. mBio, 21,12(6), e0151221. https://doi.org/10.1128/mBio.01512-21

Kosik, I., & Yewdell, J. W. (2019). Influenza Hemagglutinin and Neuraminidase: Yin⁻Yang Proteins Coevolving to Thwart Immunity. Viruses, 11(4), 346. https://doi.org/10.3390/v11040346

Krystal, M., Young, J. F., Palese, P., Wilson, I. A., Skehel, J. J., & Wiley, D. C. (1983). Sequential mutations in hemagglutinins of influenza B virus isolates: definition of antigenic domains. Proc Natl Acad Sci USA, 80(14), 4527-31. https://doi.org/10.1073/pnas.80.14.4527

Kuzmanovska, M., Boshevska, G., Janchevska, E., Buzharova, T., Simova, M., Peshnacka, A., Nikolovska, G., Kochinski, D., Ilioska, R. S., Stavridis, K., Mikikj, V., Kuzmanovska, G., Memeti, S., & Gjorgoski, I. (2021). A Comprehensive Molecular and Epidemiological Characterization of Influenza Viruses Circulating 2016-2020 in North Macedonia. Front Microbiol, 12, 713408. https://doi.org/10.3389/fmicb.2021.713408

L'Huillier, A. G., Abed, Y., Petty, T. J., Cordey, S., Thomas, Y., Bouhy, X., Schibler, M., Simon, A., Chalandon, Y., van Delden, C., Zdobnov, E., Boquete-Suter, P., Boivin, G., & Kaiser, L. (2015). E119D neuraminidase mutation conferring pan-resistance to neuraminidase inhibitors in an A(H1N1)pdm09 isolate from a stem-cell transplant recipient. J Infect Dis, 212(11), 1726-34. https://doi.org/10.1093/infdis/jiv288

Lee, H. K., Tang, J. W., Kong, D. H., Loh, T. P., Chiang, D. K-L., Lam, T. T-Y., & Koay, E. S-Ch. (2013). Comparison of mutation patterns in full-genome A/H3N2 influenza sequences obtained directly from clinical samples and the same samples after a single MDCK passage. Plos one, 8(11), e79252. https://doi.org/10.1371/journal.pone.0079252

Lee, J. M., Huddleston, J., Doud, M. B., Hooper, K. A., Wu, N. C., Bedford, T., & Bloom, J. D. (2018). Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants. Proc Natl Acad Sci USA, 115(35), E8276-E8285. https://doi.org/10.1073/pnas.1806133115

Lei, N., Wang, H., Zhang, Y., Zhong, Yi., Wang, Yj., Huang, L-y., Ma, J-xin., Sun, Q., Yang, L., & Shu, Y-long. Shu-ming Li corresponding author1 and Ling-li Suncorresponding author (2019). Molecular evolution of influenza B virus during 2011-2017 in Chaoyang, Beijing, suggesting the free influenza vaccine policy. Sci Rep, 9, 2432. https://doi.org/10.1038/s41598-018-38105-1

Li, D., Saito, R., Suzuki, Y., Sato, I., Zaraket, H., Dapat, C., Ma Caperig-Dapat, I., & Suzuki, H. (2009). In vivo and in vitro alterations in influenza A/H3N2 virus M2 and hemagglutinin genes: effect of passage in MDCK-SIAT1 cells and conventional MDCK cells. J Clin Microbiol, 47, 466-468. https://doi.org/10.1128/JCM.00892-08

Liang, W., Tan, T. J. C., Wang, Y., Lv, H., Sun, Y., Bruzzone, R., Mok, C. K. P., & Wu, N. C. (2022). Egg-adaptive mutations of human influenza H3N2 virus are contingent on natural evolution. PLoS Pathog, 18(9), e1010875. https://doi.org/10.1371/journal.ppat.1010875

Liu, Y., Wang, Y., Liu, B., Cong, X., Ji, Y., Guo, X., & Gao, Y. (2020). Phylogenetic analysis and clinical characteristics of the co-occurring mutations in HA and NA genes of influenza A(H1N1)pdm09 viruses during 2015-2017 in Beijing, China. Virol J, 17(1), 182. https://doi.org/10.1186/s12985-020-01446-3

Liu, B., Wang, Y., Liu, Y., Chen, Y., Liu, Y., Cong, X., Ji, Y., & Gao, Y. (2021). Molecular evolution and characterization of hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 viruses isolated in Beijing, China, during the 2017-2018 and 2018-2019 influenza seasons. Arch Virol, 166(1), 179-189. https://doi.org/10.1007/s00705-020-04869-z

Liu, Y., Tan, H. X., Koutsakos, M., Jegaskanda, S., Esterbauer, R., Tilmanis, D., Aban, M., Kedzierska, K., Hurt, A. C., Kent, St. J., & Wheatley, A. K. (2019). Cross-lineage protection by human antibodies binding the influenza B hemagglutinin. Nat Commun, 10, 324. https://doi.org/10.1038/s41467-018-08165-y

Liu, Y., Wang, Y., Wang, Y., Huan, Mai., Chen, Y. Y., Zhang, Y. J. Y., Cong, X., & Gao, Y. (2023). Phylogenetic analysis of HA and NA genes of influenza A viruses in immunosuppressed inpatients in Beijing during the 2018-2020 influenza seasons. Virol J, 20, 101. https://doi.org/10.1186/s12985-023-02067-2

Mancini, N., Solforosi, L., Clementi, N., de Marco, D., Clementi, M., & Burioni, R. (2011). A potential role for monoclonal antibodies in prophylactic and therapeutic treatment of influenza. Antiviral Re, 92, 15-26. https://doi.org/10.1016/j.antiviral.2011.07.013

Mao, H. Y., Sun, Y., Zhang, Y. J., Zhou, M., Chen, Y., Li, Z., Lu, Y. Y. (2013).[Analysis of genetic variation of hemagglutinin and three internal genes of influenza B virus isolated in Zhejiang province from 1999 to 2012]. [Article in Chinese]. Zhonghua Yu Fang Yi Xue Za Zhi, 47(5), 408-14.

Meijer, A., Lackenby, A., Hungnes, O., Lina, B., Werf, S. van der, Schweiger, B., Opp, M., Paget, J., Kassteele, J. van de, Hay, A., & Zambon, M. (2009). Oseltamivir-resistant influenza virus A(H1N1), Europe, 2007-08 season. Emerg Infect Dis, 15(4), 552-560. https://doi.org/10.3201/eid1504.181280

Melidou, A., Gioula, G., Exindari, M., Chatzidimitriou, D., & Malisiovas, N. (2015). Genetic analysis of post-pandemic 2010−2011 influenza A(H1N1)pdm09 hemagglutinin virus variants that caused mild, severe, and fatal infections in northern Greece. J Med Virol, 87(1), 57-67. https://doi.org/10.1002/jmv.23990

Melidou, A., Gioula, G., Exindari, M., Ioannou, E., Gkolfinopoulou, K., Georgakopoulou, T., Tsiodras, S., & Papa, A. (2017). Ιnfluenza A (H3N2) genetic variants in vaccinated patients in northern Greece. J Clinical Virology, 94, 29-32. https://doi.org/10.1016/j.jcv.2017.07.003

Melidou, A., Ködmön, C., Nahapetyan, K., Kraus, A., Alm, E., Adlhoch, C., Mooks, P., Dave, N., Carvalho, C., Meslé, M. M., Daniels, R., & Pebody, R. (2022). Members of the WHO European Region influenza surveillance network

Members of the WHO European Region influenza surveillance network that contributed virus characterisation data. Influenza returns with a season dominated by clade 3C.2a1b.2a.2 A(H3N2) viruses, WHO European Region, 2021/22. Euro Surveill, 27(15), 2200255.

Mohan, T., Nguyen, H. T., Kniss, K., Mishin, V. P., Merced-Morales, A. A., Laplante, J....Gubareva, L.V. (2021). Cluster of Oseltamivir-Resistant and Hemagglutinin Antigenically Drifted Influenza A(H1N1)pdm09 Viruses, Texas, USA, January 2020. Emerging Infectious Diseases, 27(7), 1953-1957. https://doi.org/10.3201/eid2707.204593

Moules, V., Ferraris, O., Terrier, O., Giudice, E., Yver, M., Rolland, J. P., Bergeron, C., Ottmann, M., Fournier, E. …….. & Lina, B. (2010). In vitro characterization of naturally occurring influenza H3NA- viruses lacking the NA gene segment: Toward a new mechanism of viral resistance? Virology, 404, 215-224. https://doi.org/10.1016/j.virol.2010.04.030

Njouom, R., Mba, S.A., Noah, D.N., Gregory, V., Collins, P., Cappy, P., Hay, A., & Rousse,t D. (2010). Circulation of human influenza viruses and emergence of Oseltamivir-resistant A(H1N1) viruses in Cameroon, Central Africa. BMC Infect Dis, 8, 10, 56. doi: 10.1186/1471-2334-10-56. https://doi.org/10.1186/1471-2334-10-56

Owuor, D. C., de Laurent, Z. R., Nyawanda, B. O., Emukule, G. O., Kondor, R., Barnes, J. R. D., Nokes, J., Agoti, C. N., & Chaves, S. S. (2023). Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009-2018 influenza seasons. Sci Rep, 13, 22342. https://doi.org/10.1038/s41598-023-49157-3

Pappas, C., Viswanathan, K., Chandrasekaran, A., Raman, R., Katz, J. M., Sasisekharan, R., & Tumpey, T. M. (2010). Receptor specificity and transmission of H2N2 subtype viruses isolated from the pandemic of 1957. PLoS ONE, 5, e11158. https://doi.org/10.1371/journal.pone.0011158

Park, Y. W., Kim, Y. H., Jung, H. U., Jeong, O. S., Hong, E. J., Kim, H., & Lee, J. I. (2020). Comparison of antigenic mutation during egg and cell passage cultivation of H3N2 influenza virus. Clin Exp Vaccine Res, 9(1), 56-63. https://doi.org/10.7774/cevr.2020.9.1.56

Pascalis, H., Temmam, S., Wilkinson, D. A., Dsouli, N., Turpin, M., de Lamballerie, X., & Dellagi, K. (2012). Molecular evolutionary analysis of pH1N1 2009 infuenza virus in Reunion Island, South West Indian Ocean region: a cohort study. PLoS ONE, 7(8), e43742. https://doi.org/10.1371/journal.pone.0043742

Russell, R. J., Haire, L. F., Stevens, D. J., Collins, P. J., Lin, Y. P., Blackburn, G. M., Hay, A. J., Gamblin, S. J., & Skehel, J. J. (2006). The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design. Nature, 44, 45-49. https://doi.org/10.1038/nature05114

Shtyrya, Y. A., Mochalova, L. V., & Bovin, N. V. (2009). Influenza virus neuraminidase: structure and function. Acta Naturae, 1(2), 26-32. https://doi.org/10.32607/20758251-2009-1-2-26-32

Shu, B., Kirby, M. K., Warnes, C., Sessions, W. M., Davis, W. G., Liu, J., Wilson, M. M., Lindstrom, S., Wentworth, D. E., & Barnes, J. R. (2020). Detection and discrimination of,influenza B Victoria lineage deletion variant viruses by real-time RT-PCR. Euro Surveill, 25(41), 1900652. https://doi.org/10.2807/1560-7917.ES.2020.25.41.1900652

Sriwilaijaroen, N., & Suzuki, Y. (2012). Molecular basis of the structure and function of H1 hemagglutinin of influenza virus. Proc Jpn Acad Ser B Phys Biol Sci, 88(6), 226-49. https://doi.org/10.2183/pjab.88.226

Stevens J., Blixt, O., Glaser, L., Taubenberger, J. K., Palese, P., Paulson, J. C., & Wilson, I. A. (2006). Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities. J Mol Biol, 355(5), 1143-55. https://doi.org/10.1016/j.jmb.2005.11.002

Su, S., Fu, X., Li, G., Kerlin, F., & Veit, M. (2017). Novel Influenza D virus: Epidemiology, pathology, evolution and biological characteristics. Virulence, 8(8), 1580-1591. https://doi.org/10.1080/21505594.2017.1365216

Sun, H., Wang, Y., Liu, H., Pang, Z., Cui, X., Zhao, R., Liu, Y., Qu, X., Huang, M., Ke, C., & Liao, M. (2023). The genetic diversity, replication, and transmission of 2009 pandemic H1N1 viruses in China. Front Microbiol, 14, 1110100. https://doi.org/10.3389/fmicb.2023.1110100

Tumpey, T. M., Maines, T. R., Van Hoeven, N., Glaser, L., Solórzano, A., Pappas, C., Cox, N. J., Swayne, D. E., Palese, P., Katz, J. M., & García-Sastre, A. (2007). A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science, 2, 315(5812), 655-9. https://doi.org/10.1126/science.1136212

Varghese, J. N., & Colman, P. M. (1991). Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 Å resolution. J Mol Biol, 221, 473-486. https://doi.org/10.1016/0022-2836(91)80068-6

Virk, R. K., Jayakumar, J., Mendenhall, I. H., Moorthy, M., Lam, P., Linster, M., Lim, J., Lin, C., Oon, L. L.E., Lee, H. K., Koay, E. S. C., Vijaykrishna, D., Smith, G. J. D., & Su, Y. C. F. (2020). Divergent evolutionary trajectories of influenza B viruses underlie their contemporaneous epidemic activity. Proc Natl Acad Sci USA, 117(1), 619-628. https://doi.org/10.1073/pnas.1916585116

Wang, D., Wang, J., Bi, Y., Fan, D., Liu, H., Luo, N., Yang, Z., Wang, S., Chen, W., Wang, J., Xu, S., Chen, J., Zhang, Yi., & Yin, Y. (2018). Characterization of avian influenza H9N2 viruses isolated from ostriches (Struthio camelus) Sci Rep, 8, 2273. https://doi.org/10.1038/s41598-018-20645-1

Wang, W., DeFeo, C. J., Alvarado-Facundo, E., Vassell, R., & Weiss, C. D. (2015). Intermonomer interactions in hemagglutinin subunits HA1 and HA2 affecting hemagglutinin stability and influenza virus infectivity. J Virol, 89, 10602-10611. https://doi.org/10.1128/JVI.00939-15

Wen, F., Li, L., Zhao, N., Chiang, M. J., Xie, H., Cooley, J., Webby, R., Wang, P. G., & Wan, X. F. (2018). A Y161F Hemagglutinin Substitution Increases Thermostability and Improves Yields of 2009 H1N1 Influenza A Virus in Cells. J Virol, 92(2), e01621-17. https://doi.org/10.1128/JVI.01621-17

World Health Organization (15 March 2022) Celebrating 70 years of the Global Influenza Surveillance and Response System. Available at: https://www.who.int/news-room/feature-stories/detail/celebrating-70-years-of-the-global-influenza-surveillance-and-response-system

Wu, N. C., & Wilson, I. A. (2020). Structural Biology of Influenza Hemagglutinin: An Amaranthine Adventure. Viruses, 12(9), 1053. https://doi.org/10.3390/v12091053

Wu, N. C., Otwinowski, J., Thompson, A. J., Nycholat, C. M., Nourmohammad, A., & Wilson, I. A. (2020). Major antigenic site B of human influenza H3N2 viruses has an evolving local fitness landscape. Nat Commun, 11, 1233. https://doi.org/10.1038/s41467-020-15102-5

Xing, L., Chen, Y. B., Chen, B. Q., Bu, L., Liu, Y., Zeng, Z. Q.,... & 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. https://doi.org/10.1007/s12250-021-00401-y

Xu, R., McBride, R., Paulson, J. C., Basler, C. F., & Wilson, I. A. (2010). Structure, receptor binding, and antigenicity of influenza virus hemagglutinins from the 1957 H2N2 pandemic. J Virol, 84(4), 1715-21. https://doi.org/10.1128/JVI.02162-09

Xu, R., McBride, R., Nycholat, C. M., Paulson, J. C., & Wilson, I. A. (2012). Structural characterization of the hemagglutinin receptor specificity from the 2009 H1N1 influenza pandemic. J Virol, 86(2), 982-90. https://doi.org/10.1128/JVI.06322-11

Xu, S., Zhou, J., Liu, K., Liu, Q., Xue, C., Li, X., Zheng, J., Luo, D., Cao, Y. (2013). Mutations of two transmembrane cysteines of hemagglutinin (HA) from influenza A H3N2 virus affect HA thermal stability and fusion activity. Virus Genes, 47(1), 20-26. doi: 10.1007/s11262-013-0924-0. https://doi.org/10.1007/s11262-013-0924-0

Xu, S., Zhou, J., Liu, Q., Liu, K., Xue, C., Li, X., Zheng, J., Luo, D., & Cao, Y. (2014). Evidences for the existence of intermolecular disulfide-bonded oligomers in the H3 hemagglutinins expressed in insect cells. Virus Genes, 48, 304-311. https://doi.org/10.1007/s11262-013-1021-0

Ye, F., Chen, X. J., Guan, W. D., Pan, S. H., Yang, Z. F., & Chen, R. C. (2018). Analysis of influenza B virus lineages and the HA1 domain of its hemagglutinin gene in Guangzhou, southern China, during 2016. Virol. J, 15(1), 175. https://doi.org/10.1186/s12985-018-1085-5

Zeng, Z., Yau, L-F., Lin, Z., Xia, X., Yang, Z., Wang, J-R., Song, W., & Wang, X. (2020). Characterization and Evolutionary Analysis of a Novel H3N2 Influenza A Virus Glycosylation Motif in Southern China. Front Microbiol, 11, 1318. https://doi.org/10.3389/fmicb.2020.01318

Zhao, X. N., Zhang, H. J., Li, D., Zhou, J. N., Chen, Y. Y., Sun, Y. H., Adeola, A. C., Fu, X. Q., Shao, Y., & Zhang, M. L. (2020). Whole-genome sequencing reveals origin and evolution of influenza A(H1N1)pdm09 viruses in Lincang, China, from 2014 to 2018. PLoS One, 15(6), e0234869. https://doi.org/10.1371/journal.pone.0234869

Zhang, Y., Xu, C., Zhang, H., Liu, G. D., Xue, C., & Cao, Y. (2019). Targeting Hemagglutinin: Approaches for Broad Protection against the Influenza A Virus. Viruses, 11(5), 405. https://doi.org/10.3390/v11050405

Zhou, J., Xu, S., Ma, J., Lei, W., Liu, K., Liu, Q., Ren, Y., Xue, C., & Cao, Y. (2014). Recombinant influenza A H3N2 viruses with mutations of HA transmembrane cysteines exhibited altered virological characteristics. Virus Genes, 48, 273-282. https://doi.org/10.1007/s11262-013-1011-2

Zimmer, S. M., & Burke, D. S. (2009). Historical perspective-Emergence of influenza A (H1N1) viruses. N Engl J Med, 361, 279-285. https://doi.org/10.1056/NEJMra0904322

Zost, S. J., Parkhouse, K., Gumina, M. E., Kim, K., Diaz P. S., Wilson, P. C., Treanor, J. J., Sant, A. J., Cobey, S., & Hensley, S. E. (2017). Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci USA, 114(47), 12578-12583. https://doi.org/10.1073/pnas.1712377114

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2026-05-28

How to Cite

Zadorozhna, V., Liulchuk, M., Shahinian, V., Serheieva, T., Vynnyk, N., Vynograd, N., & Marychev, I. (2026). Effect of Mutations in Hemagglutinin and Neurominidase on the Properties of Seasonal Influenza Viruses. Mikrobiolohichnyi Zhurnal, 88(1), 104-126. https://doi.org/10.15407/microbiolj88.01.104