广州市2019年H3N2流感病毒分子流行特征分析

Molecular-related epidemic characteristics of influenza A(H3N2)viruses in Guangzhou,2019

目的:对广州市2019年不同来源的H3N2流感病毒进行基因测序,分析H3N2流感病毒的进化变异特点。方法:对广州市2019年门诊监测、暴发疫情、住院重症病例等不同标本来源的H3N2流感病毒进行分离并对其血凝素(HA)和神经氨酸酶(NA)基因进行测序,运用DNA Star 7.1、Mega 6.0软件分析病毒的变异和进化特点。结果:2019年广州市H3N2流感表现为流行期Ⅰ(2019年1-8月)和流行期Ⅱ(2019年11-12月)2个流行高峰。男性和女性的H3N2流感病毒阳性率分别为13.46%(703/5221)和11.50%(510/4435),差异有统计学意义(χ2=8.43,P=0.00)。10~20岁年龄组H3N2流感病毒阳性率最高(25.18%,665/2641),各年龄组阳性率差异有统计学意义。测序发现,不同标本来源的毒株高度同源,亲缘关系相近,属于3C.2a.1分支。根据流行时间和进化特点,进一步划分为Group 1~3共3个小进化分支,Group 1分支流行于流行期Ⅰ、Group 3分支流行于流行期Ⅱ,Group 2分支为2个流行期过度的进化分支,流行期Ⅱ的病毒由流行期Ⅰ的病毒进化而来,且不同分支存在基因重组的现象。在疫苗选择压力下,Group 1~3分支逐渐出现HA抗原位点突变,导致新的抗原漂移。HA抗原位点变异主要发生A和B区,Group 1分支和Group 3分支受体结合位点变异发生在前壁和后壁,Group 2~3分支在HA抗原位点A区缺失2个糖基化位点。结论:2019年广州市H3N2流感病毒的遗传变异包括位点突变和基因重组。在疫苗免疫压力下H3N2流感病毒发生快速的进化变异,抗原位点变异逐渐累积,进而出现新的抗原漂移。应对H3N2流感病毒分子流行特点进行持续监测。

Objective To isolate the influenza A(H3N2)viruses from different sources in Guangzhou in 2019 and analyze these viruses'evolution and variation characteristics.Methods The hemagglutinin(HA)and neuraminidase(NA)genes of H3N2 isolates from outpatient monitoring,influenza outbreaks,and inpatient severe cases in Guangzhou in 2019 were sequenced.Bioinformatics software analyzed the variations and evolution characteristics of HA and NA genes.Results The epidemic peaks of influenza A(H3N2)viruses were made up of periodⅠ(from January to August)and periodⅡ(from November to December).The positive rate of influenza A(H3N2)in males was 13.46%(703/5221),which was higher than that in females(11.50%,510/4435)(χ2=8.43,P=0.00).The group's positive rate of 10-20 years old was the highest(25.18%,665/2641).The isolates from different sources were highly homologous and closely related to 3C.2a.1 branches,which could be further divided into three small groups of Group 1-3.Gene recombination was observed between different branches.The mutations of HA antigen sites gradually appeared from Group 1 to Group 3,leading to new antigen drift.Variations of HA antigenic sites mainly occurred in the region of A and B.The mutations of receptor binding sites of Group 1 and Group 3 viruses occurred in the anterior and posterior walls.There were two glycosylation sites lacked on region A of HA antigen observed in the isolates of Group 2-3.Conclusions Genetic variations of H3N2 influenza viruses in Guangzhou included gene mutations and gene recombination.Under the pressure of the vaccine,the evolution of viruses was rapid.Therefore,the monitoring of molecular-related epidemic characteristics of the H3N2 influenza virus was necessary.