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2011 年至 2021 年期间在印度流行的甲型 H1N1 流感病毒的进化动态。

Evolutionary dynamics of influenza A/H1N1 virus circulating in India from 2011 to 2021.

机构信息

Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, P-33, C.I.T, Road, Beliaghata, Kolkata 10, India.

Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, P-33, C.I.T, Road, Beliaghata, Kolkata 10, India.

出版信息

Infect Genet Evol. 2023 Jun;110:105424. doi: 10.1016/j.meegid.2023.105424. Epub 2023 Mar 11.

Abstract

Influenza A viruses (IAV) are fast-evolving pathogens with a very high mutation rate (2.0 × 10 to 2.0 × 10) compared to the influenza B (IBV) and influenza C (ICV) viruses. Generally, the tropical regions are considered as the reservoir for the IAV's genetic and antigenic evolutionary modification to be reintroduced into the temperate region. Therefore, in connection to the above facts, the present study emphasized on the evolutionary dynamic of the pandemic-2009 H1N1 (pdmH1N1) influenza virus in India. A total of Ninety-two whole genome sequences of pdmH1N1 viruses circulating in India during the 2009 post-pandemic era were analysed. The temporal signal of the study, indicating strict molecular clock evolutionary process and the overall substitution rate is 2.21 × 10/site/year. We are using the nonparametric Bayesian Skygrid coalescent model to estimates the effective past population dynamic or size over time. The study exhibits a strong relation between the genetic distances and collection dates of the Indian pdmH1N1 strain. The skygrid plot represents the highest exponential growth of IAV in rainy and winter seasons. All the genes of Indian pdmH1N1 were under purifying selective pressure. The Bayesian time-imprinted phylogenetic tree represents the following clade distributions in the country within the last 10 years; I) clade 6, 6C, and 7 were co-circulating between the 2011 to 2012 flu season; II) the clade 6B was introduced into circulation in the late seasons of 2012; III) lastly, the clade 6B remain existing in the circulation and segregated into subclade 6B.1 with five different subgroup (6B.1A, 6B.1A.1, 6B.1A.5a, 6B.1A.5a.2, 6B.1A.7). The recent circulating strain of Indian H1N1 strain represent the insertion of basic-amino acid arginine (R) in the cleavage site (325/K-R) of HA protein and amino acid mutation (314/I-M) on the lateral head surface domain of NA protein. Moreover, the study indicates the sporadic presence of the oseltamivir-resistant (275/H-Y) H1N1 variant in circulation. The present study suggests the purifying selective pressure and stochastic ecological factors for the existence and adaptation of a certain clade 6B in the host populations and additional information on the emergence of mutated strains in the circulation.

摘要

甲型流感病毒(IAV)的突变率非常高(2.0×10 到 2.0×10),与乙型流感病毒(IBV)和丙型流感病毒(ICV)相比,是一种快速进化的病原体。一般来说,热带地区被认为是 IAV 遗传和抗原进化修饰的储存库,以便重新引入温带地区。因此,鉴于上述事实,本研究强调了 2009 年大流行 H1N1(pdmH1N1)流感病毒在印度的进化动态。总共分析了印度在 2009 年大流行后期流行期间循环的 92 株 pdmH1N1 病毒的全基因组序列。研究中的时间信号表明,存在严格的分子钟进化过程,总体替代率为 2.21×10/位点/年。我们使用非参数贝叶斯 Skygrid 合并模型来估计过去的有效种群动态或随时间的大小。研究表明,印度 pdmH1N1 株的遗传距离与采集日期之间存在很强的关系。Skygrid 图表示 IAV 在雨季和冬季的最强指数增长。印度 pdmH1N1 的所有基因都受到净化选择压力的影响。贝叶斯时间印记系统发育树代表了该国在过去 10 年中的以下分支分布;I)分支 6、6C 和 7 在 2011 年至 2012 年流感季节之间共同循环;II)分支 6B 于 2012 年末季引入循环;III)最后,分支 6B 仍然存在于循环中,并分为亚分支 6B.1,有五个不同的亚群(6B.1A、6B.1A.1、6B.1A.5a、6B.1A.5a.2、6B.1A.7)。目前在印度流行的 H1N1 株代表了血凝素(HA)蛋白裂解位点(325/K-R)的碱性氨基酸精氨酸(R)插入和神经氨酸酶(NA)侧头表面结构域的氨基酸突变(314/I-M)。此外,该研究表明,在循环中存在奥司他韦耐药(275/H-Y)的 H1N1 变体。本研究表明,在宿主群体中,6B 分支的存在和适应存在净化选择压力和随机生态因素,以及循环中出现突变株的额外信息。

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