Jagadesh Anitha, Salam Abdul Ajees Abdul, Zadeh Vahid Rajabali, Krishnan Anjana, Arunkumar Govindakarnavar
Manipal Centre for Virus Research, Regional Reference Laboratory for Influenza Virus and ICMR Virology Network Laboratory, Grade I, Manipal University, Manipal, 576104, Karnataka, India.
Department of Atomic and Molecular Physics, Manipal Institute of Technology, Manipal University, Manipal, 576104, Karnataka, India.
Arch Virol. 2017 Jul;162(7):1887-1902. doi: 10.1007/s00705-017-3306-4. Epub 2017 Mar 7.
Molecular characterization of neuraminidase (NA) gene of 25 influenza A(H3N2) virus isolates (2009-2013) archived at the Manipal Centre for Virus Research was carried out. The annual rate of amino acid substitutions in the N2 gene of influenza A(H3N2) virus isolates was 0.2-0.6%. Out of the 25 NA sequences analyzed, catalytic site mutations were observed in three isolates. Two of the mutations (D151G and E276G) were detected in functional catalytic residues, and an E227V mutation was detected in the framework residues. To the best of our knowledge, NA inhibitor resistance associated with the mutations E276G and E227V has not been reported. However, the mutation D151G, which is commonly associated with culturing of influenza A(H3N2) virus in Madin-Darby canine kidney (MDCK) cells, has been reported to result in a reduction in virus susceptibility to NA inhibitor drugs. Our study also detected mutations in antigenic residues. Some of the mutations (except D197G, K249E, A250T, S334C, and H347R/N) remained conserved in isolates of succeeding seasons. Antigenic residue mutations (D197G and S334C) have not been reported globally to date. The effect of these catalytic and antigenic mutant residues on drug and antibody binding was analyzed using three-dimensional structural analysis and biochemical assays. Antigenic variability of influenza A(H3N2) viruses is a major concern, and vaccine failures are mainly due to genetic variations in the HA gene. Our study documents that genetic changes in N2 occur at a slower rate, and this information is useful for the consideration and standardization of NA in influenza vaccines.
对保存在马尼帕尔病毒研究中心的25株甲型流感病毒(H3N2)分离株(2009 - 2013年)的神经氨酸酶(NA)基因进行了分子特征分析。甲型流感病毒(H3N2)分离株N2基因的氨基酸年替换率为0.2 - 0.6%。在分析的25个NA序列中,在3个分离株中观察到催化位点突变。其中两个突变(D151G和E276G)发生在功能性催化残基上,一个E227V突变发生在框架残基上。据我们所知,与E276G和E227V突变相关的NA抑制剂耐药性尚未见报道。然而,D151G突变通常与甲型流感病毒(H3N2)在犬肾传代细胞(MDCK)中的培养有关,据报道该突变会导致病毒对NA抑制剂药物的敏感性降低。我们的研究还检测到抗原性残基的突变。部分突变(除D197G、K249E、A250T、S334C和H347R/N外)在后续季节的分离株中保持保守。抗原性残基突变(D197G和S334C)迄今尚未在全球范围内见报道。使用三维结构分析和生化分析方法分析了这些催化和抗原性突变残基对药物和抗体结合的影响。甲型流感病毒(H3N2)的抗原变异性是一个主要问题,疫苗失效主要归因于HA基因的遗传变异。我们的研究表明,N2基因的遗传变化速率较慢,该信息有助于流感疫苗中NA的考量和标准化。