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2014 至 2015 年沙特季节性 H1N1 流感病毒血凝素和神经氨酸酶的抗原漂移。

Antigenic drift of hemagglutinin and neuraminidase in seasonal H1N1 influenza viruses from Saudi Arabia in 2014 to 2015.

机构信息

Research Center, King Fahad Medical City, Riyadh, Saudi Arabia.

College of Science, King Saud University, Riyadh, Saudi Arabia.

出版信息

J Med Virol. 2020 Dec;92(12):3016-3027. doi: 10.1002/jmv.25759. Epub 2020 Apr 1.

Abstract

Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus cause a decrease in vaccine efficacy. Since the information about the evolution of these viruses in Saudi is deficient so we investigated the genetic diversity of circulating H1N1 viruses. Nasopharyngeal aspirates/swabs collected from 149 patients hospitalized with flu-like symptoms during 2014 and 2015 were analyzed. Viral RNA extraction was followed by a reverse transcription-polymerase chain reaction and genetic sequencing. We analyzed complete gene sequences of HA and NA from 80 positive isolates. Phylogenetic analysis of HA and NA genes of 80 isolates showed similar topologies and co-circulation of clades 6b. Genetic diversity was observed among circulating viruses belonging to clade 6B.1A. The amino acid residues in the HA epitope domain were under purifying selection. Amino acid changes at key antigenic sites, such as position S101N, S179N (antigenic site-Sa), I233T (antigenic site-Sb) in the head domain might have resulted in antigenic drift and emergence of variant viruses. For NA protein, 36% isolates showed the presence of amino acid changes such as V13I (n = 29), I314M (n = 29) and 12% had I34V (n = 10). However, H257Y mutation responsible for resistance to neuraminidase inhibitors was missing. The presence of amino acid changes at key antigenic sites and their topologies with structural mapping of residues under purifying selection highlights the importance of antigenic drift and warrants further characterization of recently circulating viruses in view of vaccine effectiveness. The co-circulation of several clades and the predominance of clade 6B.1 suggest multiple introductions in Saudi.

摘要

流感病毒的血凝素(HA)和神经氨酸酶(NA)蛋白的抗原漂移导致疫苗效力降低。由于沙特缺乏有关这些病毒进化的信息,因此我们研究了循环 H1N1 病毒的遗传多样性。我们分析了 2014 年和 2015 年期间因流感样症状住院的 149 名患者的鼻咽抽吸物/拭子。随后进行了病毒 RNA 提取、逆转录聚合酶链反应和基因测序。我们分析了 80 个阳性分离株的 HA 和 NA 的完整基因序列。80 个分离株的 HA 和 NA 基因的系统发育分析显示出相似的拓扑结构和 6b 分支的共同循环。属于 6B.1A 分支的循环病毒存在遗传多样性。HA 表位结构域中的氨基酸残基受到纯化选择的影响。在 HA 头部结构域的关键抗原位点,如位置 S101N、S179N(抗原位点-Sa)、I233T(抗原位点-Sb)的氨基酸变化可能导致抗原漂移和变异病毒的出现。对于 NA 蛋白,36%的分离株存在氨基酸变化,如 V13I(n=29)、I314M(n=29)和 12%的 I34V(n=10)。然而,缺失了对神经氨酸酶抑制剂有抗性的 H257Y 突变。关键抗原位点的氨基酸变化及其结构映射中受纯化选择影响的残基拓扑结构突出了抗原漂移的重要性,并需要进一步研究鉴于疫苗效果,最近循环病毒的特征。几个分支的共同循环和 6B.1 分支的优势表明在沙特多次出现病毒输入。

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