深圳市2008--2009年A型H1N1季节性流感病毒神经氨酸酶抑制剂耐药性监测

Surveillance for neuraminidase inhibitor resistance of seasonal H1N1 influenza A viruses isolated in Shenzhen during 2008 to 2009

目的对深圳市2008--2009年分离到的H1N1季节性流感病毒神经氨酸酶（NA）抑制剂的耐药性进行监测。方法根据原始临床样本的采集时间，按周抽取了55株2008--2009年分离到的H1N1季节性流感病毒，对其NA片段进行全长测序，选取WHO推荐的疫苗株和部分国内外分离到的ⅢN1季节性流感病毒作为参考株，运用Mega3．1软件进行种系发生树的构建、耐药相关位点及糖基化位点的分析。结果对NA片段的序列分析发现2008年有2株（7．1％）出现了H275Y突变，但是2009年则有25株（92．6％）出现了该突变。提示H275Y达菲耐药突变株成为了2009年深圳市社区传播的优势株。同时还发现了一株Q136K变异株，显示对乐感清出现耐药。分子进化分析结果显示，H275Y变异成为了毒株在系统进化树上分布的主要依据。所有的深圳株NA片段上潜在的糖基化位点序列保守。结论大量H275Y达菲耐药株的出现提示在今后的工作中应当密切关注流感病毒的耐药进展，进一步加强其耐药机制的研究。

Objective To analyze neuraminidase （NA） inhibitor resistance of seasonal H1 N1 influenza A viruses isolated in Shenzhen during 2008 to 2009. Methods The NA gene of these viruses were sequenced. Phylogenetic analysis of the sequences was performed with Mega3. 1 software. Results In 2008, most isolates of the seasonal H1N1 virus were susceptible to neuraminidase inhibitors, but the H275Y mutation in the neuraminidase gene region associated with high-level osehamivir resistance had been detected in 92.6% of the strains isolated in 2009. Furthermore, a strain with Q136K was found, which showed the resistance to Zanamivir. Conclusion In the light of emerging resistance, close monitoring and understanding of the nature and dynamics of resistance mutations in influenza virus should be a priority.