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分析循环狂犬病病毒株的进化、感染性和抗原性。

Analysis of the evolution, infectivity and antigenicity of circulating rabies virus strains.

机构信息

Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, People's Republic of China.

Graduate School of Peking Union Medical College, Beijing, People's Republic of China.

出版信息

Emerg Microbes Infect. 2022 Dec;11(1):1474-1487. doi: 10.1080/22221751.2022.2078742.

Abstract

Rabies virus has existed for thousands of years and is circulating in many species. In the present study, a total of 2896 rabies viruses isolated worldwide were phylogenetically classified into ten clusters based on the G gene sequence, and these clusters showed a close relationship with the hosts and regions that they were isolated from. Eighty-three representative G sequences were selected from ten clusters and were used to construct pseudoviruses using the VSV vector. The phylogenetic relationships, infectivity and antigenicity of the representative 83 pseudotyped rabies viruses were comprehensively analyzed. Eighty three pseudoviruses were divided into four antigentic clusters (GAgV), of which GAgV4 showed poor neutralization to all immunized sera. Further analysis showed that almost all strains in the GAgV4 were isolated from wild animals in the America, especially bats and skunks. No significant relationship in terms of phylogeny, infectivity and antigenicity was proved. Amino acid mutations at residues 231and 436 can affect the infectivity, while mutations at residues 113, 164 and 254 may affect the sensitivity to immunized animal sera, especially residue 254. We recommend close monitoring of infectivity and antigenicity, which should be more precise than simple genetic analysis.

摘要

狂犬病病毒已经存在了数千年,并在许多物种中传播。在本研究中,根据 G 基因序列,对全球范围内分离的 2896 株狂犬病病毒进行了系统进化分类,分为十个聚类,这些聚类与宿主和分离地密切相关。从十个聚类中选择了 83 个代表性的 G 序列,并使用 VSV 载体构建假病毒。对 83 个代表性假型狂犬病病毒的遗传进化关系、感染性和抗原性进行了综合分析。83 个假病毒分为四个抗原簇(GAgV),其中 GAgV4 对所有免疫血清的中和作用较差。进一步分析表明,GAgV4 中的几乎所有毒株均分离自美洲的野生动物,尤其是蝙蝠和臭鼬。在遗传进化、感染性和抗原性方面没有明显的关系。残基 231 和 436 处的氨基酸突变会影响感染性,而残基 113、164 和 254 处的突变可能会影响对免疫动物血清的敏感性,尤其是残基 254。我们建议密切监测感染性和抗原性,这比简单的遗传分析更精确。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9253/9176641/8d63817b40dc/TEMI_A_2078742_F0001_OC.jpg

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