Analysis of genetic characteristics of B-Victoria strains of influenza virus in Shandong Province during the influenza surveillance year from 2019 to 2020
-
摘要:
目的 了解2019—2020流感监测年度山东省B-Victoria系流感病毒流行规律及基因特征,为B型流感疫苗的接种提供参考依据。 方法 对2019—2020流感监测年度监测数据进行分析,采用多阶段抽样方法随机抽取B-Victoria系流感病毒毒株进行基因序列的测定,采用Mega X软件的Muscle方法进行多序列比对,用Neighbor-Joining方法进行系统发育分析。 结果 2019—2020流感监测年度流感病毒以B-Victoria系和H3N2亚型为主; 20株流感病毒毒株的基因进化分析表明其与同期疫苗株B/Colorado/06/2017亲缘关系较远却与下一年度疫苗株B/Washington/02/2019关系较近且共同聚集在Clade1A(Δ3)分支上,与同期疫苗株B/Colorado/06/2017相比有13处氨基酸位点改变,其中有5处位于抗原决定簇,其最大变异率为1.91%;糖基化分析显示20株流感病毒毒株全部发生209位糖基化位点增加; 20株流感病毒毒株均未发现耐药位点突变。 结论 2019—2020流感监测年度推荐疫苗保护效果可能不理想,但山东省B-Victoria系流感病毒毒株对神经氨酸酶抑制剂依旧敏感。今后应继续密切关注B-Victoria系流感病毒的流行与基因变异情况,为B型流感病毒疫苗株的推荐及B型流感的防控提供依据。 Abstract:Objective The study aims to analyze the prevalence and genetic characteristics of the B-Victoria strain of influenza virus in Shandong Province from 2019 to 2020 monitoring year, and providing a reference for the vaccination of influenza B vaccine. Methods The surveillance data of influenza surveillance from 2019 to 2020 were analyzed. B-Victoria strain of influenza were randomly selected by multi-stage sampling method for gene sequence determination, multi sequence alignment was carried out by Muscle method of Mega X software, and phylogenetic analysis was carried out by Neighbor-Joining method. Results The B-Victoria line and H3N2 subtype were the main types from 2019 to 2020 monitoring year. The phylogenetic analysis showed that the 20 strain was far from B/Colorado/06/2017, but close to B/Washington/02/2019 in the next year, and clustered on clade1A (Δ3) branch. Compared with B/Colorado/06/2017, there were 13 amino acid changes, of which 5 were located in antigenic determinants, with the maximum variation rate of 1.91%. Glycosylation analysis showed that all the 20 strains had an increase of 209 glycosylation sites, and no mutation was found in the 20 isolates. Conclusions The protective effect of the recommended vaccine from 2019 to 2020 may not be ideal, but B-Victoria strain in Shandong Province is still sensitive to neuraminidase inhibitors. We should continue to pay close attention to the prevalence and genetic variation of B-Victoria influenza virus in the future, so as to provide a basis for the recommendation and prevention of influenza B virus vaccine strains in the future. -
Key words:
- Influenza B /
- Gene characteristics /
- Hemagglutinin /
- Neuraminidase /
- Antigenicity
-
表 1 HA氨基酸位点突变情况
Table 1. HA amino acid site mutation
毒株名称 氨基酸位点 126 129 133 136 159 181 191 198 280 357 408 499 549 B/Colorado/06/2017 a N G G K A V V T R F V K T B/Washington/02/2019 b — D R E — I — N — — — R — B/Shandong-Decheng/11264/2019 — D K E — I — S — — — R — B/Shandong-Decheng/151/2020 — D K E — I — S — — — R — B/Shandong-Rencheng/133/2020 — D R E — I — N — — — R — B/Shandong-Rencheng/134/2020 — D R E — I — N — — — R — B/Shandong-Guangrao/315/2020 — D R E — I — N — — — R A B/Shandong-Rencheng/1350/2020 — D R E T I I N — L — R — B/Shandong-Rencheng/1317/2020 — D R E — I — N — — — R — B/Shandong-Tiaoqiao/3104/2019 K D R E — I — N K — I R A B/Shandong-Tiaoqiao/103/2019 K D R E — I — N K — I R A B/Shandong-Mudan/1821/2020 — D R E — I — N — — — R — B/Shandong-Shizhong/130/2020 — D R E — I — N — — — R — B/Shandong-Shizhong/121/2020 — D R G — I — N — — — R A B/Shandong-Shizhong/1874/2019 — D R E — I — N — — — R — B/Shandong-Shizhong/1914/2019 K D R E — I — N — — — R A B/Shandong-Shizhong/1904/2019 — D R E — I — N — — — R — B/Shandong-Dongying/160/2020 — D R E — I — N — — — R A B/Shandong-Jiaxiang/311/2019 — D R E — I — N — — — R — B/Shandong-Huancui/11225/2019 — N R E — I — N — — — R A B/Shandong-Dongying/1593/2019 — D K E — I — N — — — R — B/Shandong-Decheng/1394/2019 — D R E — I — N — — — R A 注:a为WHO推荐2019—2020年北半球B型流感病毒疫苗株,b为WHO推荐2020—2021年北半球B型流感病毒疫苗株,各个字母表示不同的氨基酸。A:丙氨酸;D:天冬氨酸;E:谷氨酸;G:甘氨酸;K:赖氨酸;L:亮氨酸;M:甲硫氨酸;N:天冬酰胺;P:脯氨酸;Q谷氨酰胺;R:精氨酸;S:丝氨酸;T:苏氨酸;V:缬氨酸。 -
[1] Wu P, Goldstein E, Ho LM, et al. Excess mortality associated with influenza A and B virus in Hong Kong, 1998-2009[J]. J Infect Dis, 2012, 206(12): 1862-1871. DOI: 10.1093/infdis/jis628. [2] Su S, Chaves SS, Perez A, et al. Comparing clinical characteristics between hospitalized adults with laboratory-confirmed influenza A and B virus infection[J]. Clin Infect Dis, 2014, 59(2): 252-255. DOI: 10.1093/cid/ciu269. [3] Vijaykrishna D, Holmes EC, Joseph U, et al. The contrasting phylodynamics of human influenza B viruses[J]. Elife, 2015, 4: e05055. DOI: 10.7554/eLife.05055. [4] Rota PA, Wallis TR, Harmon MW, et al. Cocirculation of two distinct evolutionary lineages of influenza type B virus since 1983[J]. Virology, 1990, 175(1): 59-68. DOI: 10.1016/0042-6822(90)90186-u. [5] 齐顺祥, 韩光跃, 刘艳芳, 等. 河北省2004—2008年乙型流行性感冒病毒监测与血凝素蛋白基因序列分析[J]. 中国疫苗和免疫, 2009, 15(1): 27-30. PMID: 20077671. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM200901010.htmQi SX, Han GY, Liu YF, et al. Virological surveillance and molecular characteristics of influenza B viruses in Hebei Province during 2004-2008[J]. Chin J Vaccines Immun, 2009, 15(1): 27-30. PMID: 20077671. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM200901010.htm [6] Cox NJ, Subbarao K. Global epidemiology of influenza: past and present[J]. Annu Rev Med, 2000, 51: 407-421. DOI: 10.1146/annurev.med.51.1.407. [7] Yan YQ, Ou JX, Zhao S, et al. Characterization of influenza A and B viruses circulating in Southern China during the 2017-2018 season[J]. Front Microbiol, 2020, 11: 1079. DOI: 10.3389/fmicb.2020.01079. [8] Lo YC, Chuang JH, Kuo HW, et al. Surveillance and vaccine effectiveness of an influenza epidemic predominated by vaccine-mismatched influenza B/Yamagata-lineage viruses in Taiwan, 2011-12 season[J]. PLoS One, 2013, 8(3): e58222. DOI: 10.1371/journal.pone.0058222. [9] Arencibia A, Piñón A, Acosta B, et al. Vaccine-mismatched influenza B/Yamagata lineage viruses in Cuba, 2012-2013 season[J]. Infect Genet Evol, 2018, 58: 110-114. DOI: 10.1016/j.meegid.2017.12.004. [10] Kumar S, Stecher G, Li M, et al. MEGA X: molecular evolutionary genetics analysis across computing platforms[J]. Mol Biol Evol, 2018, 35(6): 1547-1549. DOI: 10.1093/molbev/msy096. [11] 陈国清, 李春香, 王瑶, 等. 2015—2017年盐城市乙型流感病毒HA1、NA基因分子特征[J]. 中华疾病控制杂志, 2020, 24(2): 145-150. DOI: 10.16462/j.cnki.zhjbkz.2020.02.005.Chen GQ, Li CX, Wang Y, et al. Molecular characteristics of hemagglutinin 1 and neuraminidase genes of influenza B virus in Yancheng city from 2015 to 2017[J]. Chin J Dis Control Prev, 2020, 24(2): 145-150. DOI: 10.16462/j.cnki.zhjbkz.2020.02.005. [12] 彭晓旻, 崔淑娟, 赵佳琛, 等. 2017—2018年北京市乙型流感病毒Victoria系HA的抗原性及基因特性分析[J]. 中华实验和临床病毒学杂志, 2019, 33(4): 337-341. DOI: 10.3760/cma.j.issn.1003-9279.2019.04.001.Peng XM, Cui SJ, Zhao JC, et al. Antigenicity and genetic characterization of HA gene in influenza B/Victoria-lineage virus in Beijing 2017-2018[J]. Chin J Exp Clin Virol, 2019, 33(4): 337-341. DOI: 10.3760/cma.j.issn.1003-9279.2019.04.001. [13] Shen J, Kirk BD, Ma JP, et al. Diversifying selective pressure on influenza B virus hemagglutinin[J]. J Med Virol, 2009, 81(1): 114-124. DOI: 10.1002/jmv.21335. [14] Wang QH, Cheng F, Lu MY, et al. Crystal structure of unliganded influenza B virus hemagglutinin[J]. J Virol, 2008, 82(6): 3011-3020. DOI: 10.1128/JVI.02477-07. [15] 马建敏, 程栋, 李华峰, 等. 2012—2019年新乡市B型流感病毒基因的变异及流行趋势[J]. 中华疾病控制杂志, 2019, 23(11): 1375-1379. DOI: 10.16462/j.cnki.zhjbkz.2019.11.015.Ma JM, Chen D, Li HF, et al. Genetic variations and epidemiological characteristics of influenza B virus in Xinxiang from 2012 to 2019[J]. Chin J Dis Control Prev, 2019, 23(11): 1375-1379. DOI: 10.16462/j.cnki.zhjbkz.2019.11.015. [16] Ni F, Kondrashkina E, Wang Q. Structural basis for the divergent evolution of influenza B virus hemagglutinin[J]. Virology, 2013, 446(1-2): 112-122. doi: 10.1016/j.virol.2013.07.035. [17] Lampejo T. Influenza and antiviral resistance: an overview[J]. Eur J Clin Microbiol Infect Dis, 2020, 39(7): 1201-1208. DOI: 10.1007/s10096-020-03840-9. [18] Colman PM, Varghese JN, Laver WG. Structure of the catalytic and antigenic sites in influenza virus neuraminidase[J]. Nature, 1983, 303(5912): 41-44. DOI: 10.1038/303041a0. [19] Tafalla M, Buijssen M, Geets R, et al. A comprehensive review of the epidemiology and disease burden of Influenza B in 9 European countries[J]. Hum Vaccin Immunother, 2016, 12(4): 993-1002. DOI: 10.1080/21645515.2015.1111494. [20] 王晴, 张慕丽, 秦颖, 等. 2011—2019年中国B型流感季节性、年龄特征和疫苗匹配度分析[J]. 中华流行病杂志, 2020, 41(11): 1813-1817. DOI: 10.3760/cma.j.cn112338-20200318-00375.Wang Q, Zhang ML, Qin Y, et al. Analysis on seasonality, age distribution of influenza B cases and matching degree of influenza B vaccine in China, 2011-2019[J]. Chin J Epidemiol, 2020, 41(11): 1813-1817. DOI: 10.3760/cma.j.cn112338-20200318-00375.