浙江省1998-2005年甲3亚型流感病毒株HA1区和NA区基因特性分析

目的分析近几年浙江省甲3亚型流行性感冒（流感）流行株血凝素（HA）和神经氨酸酶（NA）基因的特性、变异与流感流行的关系。方法选择浙江省1998—2005年流感流行期间分离的甲3亚型代表株25株，提取病毒RNA，扩增HA1和NA基因，进行序列测定，用BioEdit软件分析处理。结果浙江省近几年甲3亚型流感流行株在HA1区的核苷酸长度均为987bp，编码329个氨基酸；在NA区的核苷酸长度为1362bp，编码454个氨基酸。1998—2005年甲3亚型流感病毒HA1区与NA区的氨基酸同源性分别在90．9％～99．3％与95．2％～99．5％之间，HA1区的变异较NA区更大。这8年间在HA1区共发生了30个氨基酸的替代，其中14个氨基酸位点涉及HA1区的4个抗原决定簇；NA区发生了21个氨基酸替代，其中5个氨基酸位点涉及NA区的3个抗原决定簇。在1998与2002年无论是HA1区还是NA区，均产生了较大的变异，在氨基酸进化树上也形成了独立的分支。近年的甲3亚型毒株HA1区有11个糖基化位点，较早期毒株A/Aichi／2／68增加了5个，仅1998年至今的8年中就增加了3个。结论浙江省1998与2002年的二次较大规模的甲3亚型流感流行均与病毒的抗原性漂移有关。

(knetic analysis on HAl and NA regions of influenza Virus subtype A3 isolates of Zhejiang proVince during1998-2005

Objective To study the relationship between influenza epidemic and genetic characteristic on HA and NA regions of influenza virus subtype A3 isolates of Zhejiang province in the recent years. Methods RNA of 25 influenza virus subtype A3 isolates, circulated in Zhejiang province during 1998 to 2005, was extracted. HA1 and NA regions were amplified and sequenced. All the sequence data were analyzed using BioEdit. Results HA1 and NA regions of all the isolates belonged to 987nt and 1362nt, encoding protein of 329 and 454 amino acids respectively. Isolates shared amino acid homology of 90.9%- 99.3 % and 95.2 %-99.5 % on HA1 and NA regions, while divergence on HA1 was greater than that on NA region. During a period of 8 years,30 amino acids on HA1 region were substituted and 14 of which refer to 4 antigenic determinant sites. Meanwhile,21 amino acids on NA region were substituted and 5 of which referred to 3 antigenic determinant sites. Significant divergences, both in HA1 and NA, were observed among isolates in 1998 and 2002, showing that they belonged to absolutely different branches. Additionally, influenza virus subtype A3 isolates identified in recent years, with 11 N-linked glyeosylation sites in HA1 region, had 5 sites more than early A]Aichi/2/68 strain. Since 1998,3 sites had been inserted in epidemic strains, indicating the accelerated trend of glyeosylation sites were increasing. Conclusion There is a correlation between antigenic drift of influenza virus subtype A3 and the two epidemics in Zhejiang province in 1998 and 2002.