Genetic characteristics of HA gene of influenza A (H1N1) virus isolated from severe and fatal infection cases in Guizhou province in 2019
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摘要:
目的 了解贵州省甲型H1N1流感重症或死亡病例毒株HA基因的分子特征，探讨其特异性分子位点，为流感防控提供科学依据。 方法 采集2019年贵州省甲型H1N1流感重症或死亡病例的28份鼻咽拭子标本进行病毒株的分离，其中13株病毒的HA基因被扩增和测序，利用国家生物技术信息中心或全球禽流感数据共享倡议提供的参考序列和已有的轻症病例毒株序列对HA基因进行生物信息学分析。 结果 2019年贵州省甲型H1N1流感重症或死亡病例毒株核苷酸和氨基酸同源性分别为98.0%～100.0%和97.9%～100.0%，分别处于不同次分支；与2019年和既往疫苗株相比，核苷酸和氨基酸同源性分别为98.2%～99.3%、97.1%～98.4%和98.1%～98.9%、97.5%～98.7%；与轻症病例相比，重症或死亡病例毒株共发生了12个位点的突变，其中V312I为共有的突变位点，抗原决定簇突变共涉及到3个区域，毒株QNZ2019YYX和BJ2019WXP发生了2个位点的突变。 结论 2019年度疫苗株匹配性更高，部分毒株突变涉及到抗原决定簇的2个区域，可能为新的变异株，V3121位点可能为重症或死亡病例毒株的特异性分子位点，需进一步研究和加强实时监测。 -
关键词:
- 甲型H1N1流感病毒 /
- HA基因 /
- 重症或死亡病例 /
- 分子特征
Abstract:Objective To analyze characteristics and specific molecular sites of hemagglutinin (HA) gene of influenza A (H1N1) virus isolated among severe and deadly infection cases in Guizhou province in 2019 for providing evidence to influenza prevention and control in the province. Methods Influenza A (H1N1) virus strains were isolated from 28 nasopharyngeal swab specimens collected from severe and fatal infection incidents in the province during 2019. HA genes of the 13 isolated viral strains were amplified and sequenced. Bioinformatics analysis was performed on the HA genes using existing sequence of strains in mild cases and reference sequences from National Center of Biotechnology Information (NCBI) or the Global Initiative on Sharing Avian Influenza Data (GISAID). Results The homology of the nucleotide and amino acid sequences are 98.0% – 100.0% and 97.9% – 100.0% among the isolated virus strains and the strains belong to different secondary branches. In comparison with those of the vaccine strain of 2019 and previous years, the homology of the nucleotide/amino acid sequences of the isolated strains are 98.2% – 99.3%/97.1% – 98.4% and 98.1% – 98.9%/97.5% – 98.7%, respectively. Contrasted to those of mild infection cases, a total of 12 gene locus mutations were identified in the isolated virus strains and V312I was a common locus of the mutations. Antigen determinant mutations in 3 gene regions were identified, with 2 simultaneous mutations among loci of strains QNZ2019YYX and BJ2019WXP. Conclusion The homology of HA gene sequences is high between influenza A (H1N1) virus strains isolated among severe and fatal infection cases in Guizhou province and the vaccine strain in 2019. Mutations of the isolated virus strains involved two antigen determinants and the strains may be novel variants. The mutant V312I may be a specific locus for pathogenicity of the isolated virus strains. -
图 1 贵州省2019年甲型H1N1流感病毒株HA基因遗传进化树
注：▲代表贵州省甲型H1N1流感重症或死亡病例毒株；●代表疫苗株。
Figure 1. Genetic evolution tree of the HA gene of influenza A (H1N1) virus strain isolated in Guizhou province in 2019
表 1 贵州省2019年新甲型H1N1流感病毒株HA基因氨基酸位点突变情况
Table 1. Amino acid site mutations of the HA gene of influenza A (H1N1) virus isolated in Guizhou Province in 2009
毒株编号 氨基酸突变位点 5 62 63 121 146 158 a 173 a 200 202 a 204 a 226 b 251 277 278 303 308 312 1 L R G Q N A N S T D K V N A I P I 2 L G G Q N A N P T D K V N A I P V 3 L R G Q N A N S I D K V N A L P V 4 L R G Q N A N P T D K V N A I P V 5 L R G Q N A N P T D K V N A I P V 6 L R G Q D A N P I D K V D A I P V 7 L R G Q D A N P I D K V D A I P V 8 L R G Q D A N P I D K V D A I P V 9 L R G Q D A N P I D K V D A I P V 10 L R R Q N A N P T D K V N D I P I 11 L R G Q N A N P T D K V N D I P I 12 L R G Q N A N P T D K V N D I S I 13 L R G Q N A N P T D K V N D I P I 14 L R G H N A N S I D K V N A L P I 15 L R G Q D A N P I D K V D A I P I 16 L G G Q D A N P I V K V D A I P I 17 L R G Q D A N P I D K V D A I P I 18 L R G Q D A K P I D Q V D A I P I 19 I R G Q D A N P I D K V D A I P I 20 L R G Q D A N P I D K V D A I P I 21 L R G Q N A N P I D K V N A I P I 22 L R G Q D E N P T D K L N D I P I 23 L R G Q D A N P I D K V D A I P V 24 L R G Q N A N P T D K V N A I P V 25 L R G Q N A N S T D K V N A I P V 26 L R G Q N A N P I D K V N A I P V 27 L R G Q N A N S T D K V N A I P V 注：a 抗原决定簇位点；b 受体结合位点。 
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