Conflict of interest statement
All authors have no conflict of interest to declare.
Abe, Y., Takashita, E., Sugawara, K., Matsuzaki, Y., Muraki, Y., &
Hongo, S. (2004). Effect of the addition of oligosaccharides on the
biological activities and antigenicity of influenza A/H3N2 virus
hemagglutinin. J Virol, 78(18), 9605-9611.
doi:10.1128/JVI.78.18.9605-9611.2004
Baele, G., Lemey, P., Bedford, T., Rambaut, A., Suchard, M. A., &
Alekseyenko, A. V. (2012). Improving the accuracy of demographic and
molecular clock model comparison while accommodating phylogenetic
uncertainty. Mol Biol Evol, 29(9), 2157-2167. doi:10.1093/molbev/mss084
Baele, G., Li, W. L., Drummond, A. J., Suchard, M. A., & Lemey, P.
(2013). Accurate model selection of relaxed molecular clocks in bayesian
phylogenetics. Mol Biol Evol, 30(2), 239-243. doi:10.1093/molbev/mss243
Bi, Y., Li, J., Li, S., Fu, G., Jin, T., Zhang, C., . . . Shi, W.
(2020). Dominant subtype switch in avian influenza viruses during
2016-2019 in China. Nat Commun, 11(1), 5909.
doi:10.1038/s41467-020-19671-3
Crowe, J. E., Jr. (2012). Influenza virus resistance to human
neutralizing antibodies. mBio, 3(4), e00213-00212.
doi:10.1128/mBio.00213-12
Das, S. R., Hensley, S. E., David, A., Schmidt, L., Gibbs, J. S.,
Puigbo, P., . . . Yewdell, J. W. (2011). Fitness costs limit influenza A
virus hemagglutinin glycosylation as an immune evasion strategy. Proc
Natl Acad Sci U S A, 108(51), E1417-1422. doi:10.1073/pnas.1108754108
Drummond, A. J., Nicholls, G. K., Rodrigo, A. G., & Solomon, W. (2002).
Estimating mutation parameters, population history and genealogy
simultaneously from temporally spaced sequence data. Genetics, 161(3),
1307-1320. doi:10.1093/genetics/161.3.1307
Drummond, A. J., Rambaut, A., Shapiro, B., & Pybus, O. G. (2005).
Bayesian coalescent inference of past population dynamics from molecular
sequences. Mol Biol Evol, 22(5), 1185-1192. doi:10.1093/molbev/msi103
Edgar, R. C. (2004). MUSCLE: multiple sequence alignment with high
accuracy and high throughput. Nucleic Acids Res, 32(5), 1792-1797.
doi:10.1093/nar/gkh340
Gao, R., Gu, M., Shi, L., Liu, K., Li, X., Wang, X., . . . Liu, X.
(2021). N-linked glycosylation at site 158 of the HA protein of H5N6
highly pathogenic avian influenza virus is important for viral
biological properties and host immune responses. Vet Res, 52(1), 8.
doi:10.1186/s13567-020-00879-6
Gerloff, N. A., Khan, S. U., Balish, A., Shanta, I. S., Simpson, N.,
Berman, L., . . . Davis, C. T. (2014). Multiple reassortment events
among highly pathogenic avian influenza A(H5N1) viruses detected in
Bangladesh. Virology, 450-451, 297-307. doi:10.1016/j.virol.2013.12.023
Hensley, S. E., Das, S. R., Bailey, A. L., Schmidt, L. M., Hickman, H.
D., Jayaraman, A., . . . Yewdell, J. W. (2009). Hemagglutinin receptor
binding avidity drives influenza A virus antigenic drift. Science,
326(5953), 734-736. doi:10.1126/science.1178258
Hoffmann, E., Stech, J., Guan, Y., Webster, R. G., & Perez, D. R.
(2001). Universal primer set for the full-length amplification of all
influenza A viruses. Arch Virol, 146(12), 2275-2289.
doi:10.1007/s007050170002
Jin, F., Dong, X., Wan, Z., Ren, D., Liu, M., Geng, T., . . . Ye, J.
(2019). A Single Mutation N166D in Hemagglutinin Affects Antigenicity
and Pathogenesis of H9N2 Avian Influenza Virus. Viruses, 11(8).
doi:10.3390/v11080709
Kaverin, N. V., Rudneva, I. A., Ilyushina, N. A., Lipatov, A. S.,
Krauss, S., & Webster, R. G. (2004). Structural differences among
hemagglutinins of influenza A virus subtypes are reflected in their
antigenic architecture: analysis of H9 escape mutants. J Virol, 78(1),
240-249. doi:10.1128/jvi.78.1.240-249.2004
Koel, B. F., Burke, D. F., Bestebroer, T. M., van der Vliet, S., Zondag,
G. C., Vervaet, G., . . . Smith, D. J. (2013). Substitutions near the
receptor binding site determine major antigenic change during influenza
virus evolution. Science, 342(6161), 976-979.
doi:10.1126/science.1244730
Lewis, N. S., Anderson, T. K., Kitikoon, P., Skepner, E., Burke, D. F.,
& Vincent, A. L. (2014). Substitutions near the hemagglutinin
receptor-binding site determine the antigenic evolution of influenza A
H3N2 viruses in U.S. swine. J Virol, 88(9), 4752-4763.
doi:10.1128/JVI.03805-13
Li, X., Tian, B., Jianfang, Z., Yongkun, C., Xiaodan, L., Wenfei, Z., .
. . Shu, Y. (2017). A comprehensive retrospective study of the
seroprevalence of H9N2 avian influenza viruses in occupationally exposed
populations in China. PLoS One, 12(6), e0178328.
doi:10.1371/journal.pone.0178328
Okamatsu, M., Sakoda, Y., Kishida, N., Isoda, N., & Kida, H. (2008).
Antigenic structure of the hemagglutinin of H9N2 influenza viruses. Arch
Virol, 153(12), 2189-2195. doi:10.1007/s00705-008-0243-2
Peacock, T., Reddy, K., James, J., Adamiak, B., Barclay, W., Shelton,
H., & Iqbal, M. (2016). Antigenic mapping of an H9N2 avian influenza
virus reveals two discrete antigenic sites and a novel mechanism of
immune escape. Sci Rep, 6, 18745. doi:10.1038/srep18745
Peacock, T. P., Benton, D. J., James, J., Sadeyen, J. R., Chang, P.,
Sealy, J. E., . . . Iqbal, M. (2017). Immune Escape Variants of H9N2
Influenza Viruses Containing Deletions at the Hemagglutinin Receptor
Binding Site Retain Fitness In Vivo and Display Enhanced Zoonotic
Characteristics. J Virol, 91(14). doi:10.1128/JVI.00218-17
Peacock, T. P., Harvey, W. T., Sadeyen, J. R., Reeve, R., & Iqbal, M.
(2018). The molecular basis of antigenic variation among A(H9N2) avian
influenza viruses. Emerg Microbes Infect, 7(1), 176.
doi:10.1038/s41426-018-0178-y
Peacock, T. P., Sealy, J. E., Harvey, W. T., Benton, D. J., Reeve, R.,
& Iqbal, M. (2020). Genetic determinants of receptor-binding preference
and zoonotic potential of H9N2 avian influenza viruses. J Virol.
doi:10.1128/JVI.01651-20
Poh, Z. W., Wang, Z., Kumar, S. R., Yong, H. Y., & Prabakaran, M.
(2020). Modification of neutralizing epitopes of hemagglutinin for the
development of broadly protective H9N2 vaccine. Vaccine, 38(6),
1286-1290. doi:10.1016/j.vaccine.2019.11.080
Pybus, O. G., & Rambaut, A. (2002). GENIE: estimating demographic
history from molecular phylogenies. Bioinformatics, 18(10), 1404-1405.
doi:10.1093/bioinformatics/18.10.1404
Rambaut, A., Drummond, A. J., Xie, D., Baele, G., & Suchard, M. A.
(2018). Posterior Summarization in Bayesian Phylogenetics Using Tracer
1.7. Syst Biol, 67(5), 901-904. doi:10.1093/sysbio/syy032
Santos, J. J. S., Abente, E. J., Obadan, A. O., Thompson, A. J.,
Ferreri, L., Geiger, G., . . . Perez, D. R. (2019). Plasticity of Amino
Acid Residue 145 Near the Receptor Binding Site of H3 Swine Influenza A
Viruses and Its Impact on Receptor Binding and Antibody Recognition. J
Virol, 93(2). doi:10.1128/JVI.01413-18
Song, J., Wang, C., Gao, W., Sun, H., Jiang, Z., Wang, K., . . . Pu, J.
(2020). A D200N hemagglutinin substitution contributes to antigenic
changes and increased replication of avian H9N2 influenza virus. Vet
Microbiol, 245, 108669. doi:10.1016/j.vetmic.2020.108669
Su, H., Zhao, Y., Zheng, L., Wang, S., Shi, H., & Liu, X. (2020).
Effect of the selection pressure of vaccine antibodies on evolution of
H9N2 avian influenza virus in chickens. AMB Express, 10(1), 98.
doi:10.1186/s13568-020-01036-0
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(1), vey016.
doi:10.1093/ve/vey016
Sun, Y., Cong, Y., Yu, H., Ding, Z., & Cong, Y. (2021). Assessing the
effects of a two-amino acid flexibility in the Hemagglutinin 220-loop
receptor-binding domain on the fitness of Influenza A(H9N2) viruses.
Emerg Microbes Infect, 10(1), 822-832. doi:10.1080/22221751.2021.1919566
Sun, Y., & Liu, J. (2015). H9N2 influenza virus in China: a cause of
concern. Protein Cell, 6(1), 18-25. doi:10.1007/s13238-014-0111-7
Wan, Z., Ye, J., Xu, L., Shao, H., Jin, W., Qian, K., . . . Qin, A.
(2014). Antigenic mapping of the hemagglutinin of an H9N2 avian
influenza virus reveals novel critical amino acid positions in antigenic
sites. J Virol, 88(7), 3898-3901. doi:10.1128/JVI.03440-13
Wu, N. C., & Wilson, I. A. (2020). Structural Biology of Influenza
Hemagglutinin: An Amaranthine Adventure. Viruses, 12(9).
doi:10.3390/v12091053
Xia, J., Adam, D. C., Moa, A., Chughtai, A. A., Barr, I. G., Komadina,
N., & MacIntyre, C. R. (2020). Comparative epidemiology, phylogenetics,
and transmission patterns of severe influenza A/H3N2 in Australia from
2003 to 2017. Influenza Other Respir Viruses, 14(6), 700-709.
doi:10.1111/irv.12772
Xia, J., Cui, J. Q., He, X., Liu, Y. Y., Yao, K. C., Cao, S. J., . . .
Huang, Y. (2017). Genetic and antigenic evolution of H9N2 subtype avian
influenza virus in domestic chickens in southwestern China, 2013-2016.
PLoS One, 12(2), e0171564. doi:10.1371/journal.pone.0171564
Xia, J., He, X., Yao, K. C., Du, L. J., Liu, P., Yan, Q. G., . . .
Huang, Y. (2016). Phylogenetic and antigenic analysis of avian
infectious bronchitis virus in southwestern China, 2012-2016. Infect
Genet Evol, 45, 11-19. doi:10.1016/j.meegid.2016.08.011
Xia, J., Yao, K. C., Liu, Y. Y., You, G. J., Li, S. Y., Liu, P., . . .
Huang, Y. (2017). Isolation and molecular characterization of prevalent
Fowl adenovirus strains in southwestern China during 2015-2016 for the
development of a control strategy. Emerg Microbes Infect, 6(11), e103.
doi:10.1038/emi.2017.91
Zhou, Z. J., Qiu, Y., Pu, Y., Huang, X., & Ge, X. Y. (2020). BioAider:
An efficient tool for viral genome analysis and its application in
tracing SARS-CoV-2 transmission. Sustain Cities Soc, 63, 102466.
doi:10.1016/j.scs.2020.102466
Zhu, Y., Yang, D., Ren, Q., Yang, Y., Liu, X., Xu, X., . . . Liu, X.
(2015). Identification and characterization of a novel antigenic epitope
in the hemagglutinin of the escape mutants of H9N2 avian influenza
viruses. Vet Microbiol, 178(1-2), 144-149.
doi:10.1016/j.vetmic.2015.04.012
Table 1 The titer of mutant CQY-2014 H9N2-AIVs in MDCK cells
and chicken embryos