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韩国蝙蝠冠状病毒的遗传多样性及中东呼吸综合征相关冠状病毒的比较遗传分析

Genetic diversity of bat coronaviruses and comparative genetic analysis of MERS-related coronaviruses in South Korea.

作者信息

Lee Sook-Young, Chung Chul-Un, Park Jun Soo, Kim Yoon Ji, Kim Young-Sik, Na Eun-Jee, Kim YongKwan, Oem Jae-Ku

机构信息

Laboratory of Veterinary Infectious Disease, College of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of Korea.

Department of Life Science, Dongguk University, Gyeongju, Republic of Korea.

出版信息

Transbound Emerg Dis. 2022 Jul;69(4):e463-e472. doi: 10.1111/tbed.14324. Epub 2021 Sep 30.

DOI:10.1111/tbed.14324
PMID:34536059
Abstract

Bats have been identified as a natural reservoir of several potentially zoonotic viruses, including Lyssavirus, Ebola virus, Marburg virus, Hendra virus, Nipah virus, as well as severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus (CoV). Here, we performed a molecular epidemiological investigation of South Korean bat viruses. Genetic comparative analysis was performed on the spike glycoprotein gene of the detected MERS-related CoVs. Among 1640 samples (348 oral swabs, 1199 faecal samples, 83 urine samples and 10 bat carcass) collected across 24 South Korean provinces during 2017-2019, CoV was detected in 82 samples (75 faeces and seven oral swab samples) from 11 provinces. Surveillance over the 3 years during which samples were collected revealed significantly higher CoV detection rates between spring and autumn, and a high detection rate in Vespertillionidae and Rhinolophidae bats. Our phylogenetic analysis shows that Korean bat CoVs are genetically diverse regardless of their spatiotemporal distribution and their host species, and that the discovered bat CoVs belong to various subgenera within the Alpha- and Betacoronavirus genera. Twenty detected MERS-related CoVs belonging to the genus Betacoronavirus were similar to the Ia io bat CoV NL140422 and NL13845 strains. A comprehensive genetic analysis of two Korean bat MERS-related CoV spike receptor binding domain (RBDs) (176 and 267 strains) showed that the 18 critical residues that are involved in interactions with the human DPP4 receptor are most similar to the NL13845 strain, which is known to not bind with hDPP4. A deeper analysis of the interfacing residues in the Korean bat MERS-related CoVs RBD-hDPP4 complexes showed that the Korean bat CoVs has fewer polar contacts than the NL13845 strain. Although further study will be needed, these results suggest that Korean bat MERS-related CoVs are unlikely to bind with hDPP4. Nevertheless, these findings highlight the need for continuous monitoring to identifying the origin of new infectious diseases, specifically mutant CoV.

摘要

蝙蝠已被确定为几种潜在人畜共患病毒的天然宿主,包括狂犬病病毒、埃博拉病毒、马尔堡病毒、亨德拉病毒、尼帕病毒,以及严重急性呼吸综合征和中东呼吸综合征冠状病毒(CoV)。在此,我们对韩国蝙蝠病毒进行了分子流行病学调查。对检测到的中东呼吸综合征相关冠状病毒的刺突糖蛋白基因进行了遗传比较分析。在2017年至2019年期间,从韩国24个省份采集的1640份样本(348份口腔拭子、1199份粪便样本、83份尿液样本和10具蝙蝠尸体)中,在来自11个省份的82份样本(75份粪便和7份口腔拭子样本)中检测到了冠状病毒。在采集样本的3年监测期间发现,春秋两季冠状病毒的检出率显著更高,且伏翼科和菊头蝠科蝙蝠中的检出率较高。我们的系统发育分析表明,韩国蝙蝠冠状病毒在遗传上具有多样性,无论其时空分布和宿主物种如何,并且发现的蝙蝠冠状病毒属于甲型和乙型冠状病毒属内的各个亚属。检测到的20种属于乙型冠状病毒属的中东呼吸综合征相关冠状病毒与艾氏管鼻蝠冠状病毒NL140422和NL13845毒株相似。对两种韩国蝙蝠中东呼吸综合征相关冠状病毒刺突受体结合域(RBD)(176和267毒株)的全面遗传分析表明,与人类二肽基肽酶4(DPP4)受体相互作用的18个关键残基与已知不与hDPP4结合的NL13845毒株最为相似。对韩国蝙蝠中东呼吸综合征相关冠状病毒RBD-hDPP4复合物中界面残基的深入分析表明,韩国蝙蝠冠状病毒与NL13845毒株相比具有更少的极性接触。尽管还需要进一步研究,但这些结果表明,韩国蝙蝠中东呼吸综合征相关冠状病毒不太可能与hDPP4结合。然而,这些发现凸显了持续监测以确定新传染病,特别是突变冠状病毒起源的必要性。

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