2019⁃2020年阿克苏地区A(H3N2)亚型流感病毒抗原变异与耐药分析

Antigenic Variation and Drug Resistance of the Influenza A Virus Subtype H3N2 in Aksu,China,from 2019 to 2020

为分析中国新疆阿克苏地区2019⁃2020年A(H3N2)亚型流感病毒抗原性变异及耐药情况。本文选取A(H3N2)亚型流感病毒血凝滴度≥8的毒株,用标准雪貂抗血清进行抗原性分析,利用二代测序技术对病毒基因测序后进行序列分析,通过耐药检测分析病毒对神经氨酸酶抑制剂的敏感性。抗原性分析结果显示,全部毒株为疫苗株A/Kansas/14/2017细胞株的低反应株,均为疫苗株A/HongKong/45/2019细胞株的类似株。HA和NA基因序列进化树显示与A/HongKong/45/2019属于同一分支。与同年疫苗株A/Kansas/14/2017比对,HA蛋白抗原决定簇位点氨基酸变异,分别是E62G、N91S、K92R、N121K、T135K、S137F、K144S、S159Y、K160T、N171K、I179V、R208I;受体结合位点T135K、S137F处氨基酸发生变异;133⁃135、483⁃485处减少两个潜在糖基化位点,158⁃160处增加1个潜在糖基化位点;HA蛋白二硫键位点保守。与同年疫苗A/Kansas/14/2017比对,NA蛋白抗原决定簇位点T329S、K344E处氨基酸发生变异;NA蛋白酶活性位点及周围催化位点、耐药位点、糖基化位点保守,二硫键C42F处发生氨基酸变异。M2蛋白S31N位点处氨基酸发生变异。本地区A(H3N2)流感病毒对神经氨酸酶抑制剂奥司他韦和扎那米韦药物敏感。总之,2019⁃2020年阿克苏地A(H3N2)亚型流感病毒与WHO推荐的2019⁃2020年北半球疫苗株A/Kansas/14/2017不匹配,而与WHO推荐2020⁃2021年北半球疫苗株A/HongKong/45/2019匹配性更好。还需持续做好流感病毒抗原性和耐药监测工作,及时掌握流感病毒基因特性情况,为本地区流感病毒防控提供科学依据。

We wished to analyze the antigenic variation and drug resistance of influenza A virus subtype H3N2 strains in Aksu,China,in 2019–2020.We selected influenza A virus subtype H3N2 strains with hemagglutination titer≥8 and analyzed antigenicity with reference ferret anti⁃sera.We sequenced viral genes using second⁃generation technology.The susceptibility of the virus to neuraminidase inhibitors was analyzed by a drug⁃resistance test.Antigenicity analyses showed that all strains were low⁃reactive strains of the vaccine strain A/Kansas/14/2017 cell line,and that all strains were similar to the vaccine strain A/HongKong/45/2019 cell line.The phylogenetic trees of sequences of HA and NA showed that they belonged to the same branch as A/HongKong/45/2019.Compared with the vaccine strain A/Kansas/14/2017,the variations in the amino acids of the antigen sites of HA proteins were E62G,N91S,K92R,N121K,T135K,S137F,K144S,S159Y,K160T,N171K,I179V and R208I;the amino acids at receptor binding sites T135K and S137F were mutated.Two potential glycosylation sites(133–135 and 483–485)were reduced and one potential glycosylation site(158–160)was increased.The disulfide bond site of HA protein was conserved.Compared with the vaccine strain A/Kansas/14/2017,the variation in amino acids occurred at the antigenic determinant cluster sites T329S and K344E in NA protein;the NA protease active site and its surrounding catalytic sites,drug⁃resistance sites,and glycosylation sites were conserved.Variation in amino acids occurred at the disulfide bond C42F.Variants of amino acids occurred at the S31N site of M2 protein.Influenza A virus subtype H3N2 strains in this region were sensitive to the neuraminidase inhibitors oseltamivir and zanamivir.In conclusion,the antigenicity and genetic characteristics of influenza A virus subtype H3N2 in Aksu from 2019 to 2020 have changed compared with those in the vaccine strain A/Kansas/14/2017 in the same year.The 2019–2020 Aksu subtype A(H3N2)influenza virus does not match the World Health Organization(WHO)⁃recommended 2019–2020 Northern Hemisphere vaccine A/Kansas/14/2017,but matches better with the WHO⁃recommended 2020–2021 Northern Hemisphere vaccine strain A/HongKong/45/2019.Studying the antigenicity and drug resistance of influenza viruses must be continued to ascertain their genetic characteristics.In this way,a scientific basis for the prevention and control of influenza viruses in Aksu can be obtained.