高致病性H7N9禽流感病毒神经氨酸酶R292K、E119V突变型耐药株感染MDCK细胞转录组学研究Transcriptomic Study of MDCK Cells Infected with Neuraminidase Inhibitor-resistant Strains of the Highly Pathogenic Avian Influenza H7N9 Virus Bearing R292K or E119V Substitution
唐静;张曙霞;张靖;李希妍;刘佳;王大燕;
摘要(Abstract):
人感染高致病性H7N9禽流感病毒(Highly pathogenic avian influenza H7N9,HPAI H7N9)神经氨酸酶抑制剂(Neuraminidase inhibitors,NAIs)耐药株在哺乳动物细胞中适应性较好,是其导致病死率高的原因之一。本文研究HPAI H7N9耐药株对流感病毒敏感细胞MDCK细胞转录的影响。用0.1 MOI含NAIs耐药突变位点(NA R292K,E119V)的HPAI H7N9重组病毒及其敏感株感染MDCK细胞,于感染后0h、7h和24h取样,进行RNA测序并分析。结果三株病毒感染细胞0h和7h时,各组差异表达基因(Differentially expressed genes,DEGs)较少。24h时敏感株、R292K株和E119V株感染后的DEGs均显著增加,数量相似,分别为10 508、10 663和10 711,其中三者共同DEGs为83%~85%,每组特有DEGs为3%~8%。3株病毒感染细胞24 h时DEGs涉及的KEGG通路分类及各通路下基因个数及所占比例均较相似,且3者前20条KEGG通路中多数(11条)通路相同。结果说明,含R292K或E119V耐药突变位点的HPAI H7N9病毒与其敏感株相似地能在MDCK细胞中引起较强烈的转录改变并影响细胞代谢及免疫通路。
关键词(KeyWords): 高致病性H7N9禽流感病毒;神经氨酸酶抑制剂耐药株;292K;119V;转录组学
基金项目(Foundation): 国家自然科学基金青年基金(项目号:82102370),题目:人感染高致病性H7N9禽流感病毒神经氨酸酶抑制剂耐药机制及替代药物的研究~~
作者(Authors): 唐静;张曙霞;张靖;李希妍;刘佳;王大燕;
DOI: 10.13242/j.cnki.bingduxuebao.004145
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