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血凝素中的V223I替换降低了对人型受体的结合亲和力,同时增强了H3N2犬流感病毒的热稳定性。

The V223I substitution in hemagglutinin reduces the binding affinity to human-type receptors while enhancing the thermal stability of the H3N2 canine influenza virus.

作者信息

Liu Liling, Wang Fujun, Wu Ying, Mi Weiyong, Zhang Yaping, Chen Lei, Wang Dongxue, Deng Guohua, Shi Jianzhong, Chen Hualan, Kong Huihui

机构信息

State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, CAAS, Harbin, China.

Department of Biotechnology, Heilongjiang Vocational College for Nationalities, Harbin, China.

出版信息

Front Microbiol. 2024 Jul 22;15:1442163. doi: 10.3389/fmicb.2024.1442163. eCollection 2024.

DOI:10.3389/fmicb.2024.1442163
PMID:39104583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11299061/
Abstract

Given the intimate relationship between humans and dogs, the H3N2 canine influenza viruses (CIVs) pose a threat to public health. In our study, we isolated four H3N2 CIVs from 3,758 dog nasal swabs in China between 2018 and 2020, followed by genetic and biological analysis. Phylogenetic analysis revealed 15 genotypes among all available H3N2 CIVs, with genotype 15 prevailing among dogs since around 2017, indicating the establishment of a stable virus lineage in dogs. Molecular characterization identified many mammalian adaptive substitutions, including HA-G146S, HA-N188D, PB2-I292T, PB2-G590S, PB2-S714I, PB1-D154G, and NP-R293K, present across the four isolates. Notably, analysis of HA sequences uncovered a newly emerged adaptive mutation, HA-V223I, which is predominantly found in human and swine H3N2 viruses, suggesting its role in mammalian adaptation. Receptor-binding analysis revealed that the four H3N2 viruses bind both avian and human-type receptors. However, HA-V223I decreases the H3N2 virus's affinity for human-type receptors but enhances its thermal stability. Furthermore, attachment analysis confirmed the H3N2 virus binding to human tracheal tissues, albeit with reduced affinity when the virus carries HA-V223I. Antigenic analysis indicated that the current human H3N2 vaccines do not confer protection against H3N2 CIVs. Collectively, these findings underscore that the potential threat posed by H3N2 CIVs to human health still exists, emphasizing the necessity of close surveillance and monitoring of H3N2 CIVs in dogs.

摘要

鉴于人类与狗之间的密切关系,H3N2犬流感病毒(CIVs)对公共卫生构成威胁。在我们的研究中,我们于2018年至2020年间从中国的3758份犬鼻拭子中分离出4株H3N2 CIVs,随后进行了基因和生物学分析。系统发育分析显示,在所有可用的H3N2 CIVs中存在15种基因型,自2017年左右以来,基因型15在犬类中占主导地位,这表明在犬类中已建立了稳定的病毒谱系。分子特征鉴定发现了许多哺乳动物适应性替代,包括HA-G146S、HA-N188D、PB2-I292T、PB2-G590S、PB2-S714I、PB1-D154G和NP-R293K,这些在这4株分离株中均有出现。值得注意的是,对HA序列的分析发现了一个新出现的适应性突变HA-V223I,该突变主要存在于人类和猪的H3N2病毒中,表明其在哺乳动物适应性中的作用。受体结合分析表明,这4株H3N2病毒同时结合禽源和人源受体。然而,HA-V223I降低了H3N2病毒对人源受体的亲和力,但增强了其热稳定性。此外,附着分析证实了H3N2病毒与人气管组织的结合,尽管当病毒携带HA-V223I时亲和力降低。抗原分析表明,目前的人类H3N2疫苗不能对H3N2 CIVs提供保护。总的来说,这些发现强调了H3N2 CIVs对人类健康构成的潜在威胁仍然存在,突出了对犬类中的H3N2 CIVs进行密切监测的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5151/11299061/364958ae0f03/fmicb-15-1442163-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5151/11299061/afb591c171f9/fmicb-15-1442163-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5151/11299061/c67f6868d11f/fmicb-15-1442163-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5151/11299061/2a9d58aa1d8b/fmicb-15-1442163-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5151/11299061/364958ae0f03/fmicb-15-1442163-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5151/11299061/afb591c171f9/fmicb-15-1442163-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5151/11299061/c67f6868d11f/fmicb-15-1442163-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5151/11299061/2a9d58aa1d8b/fmicb-15-1442163-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5151/11299061/364958ae0f03/fmicb-15-1442163-g004.jpg

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