组粒JN.1变异体增强反向人畜共患病潜能和免疫逃避

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-06 DOI:10.1016/j.isci.2025.112824

Jiaxin Hu , Fuwen Zan , Yixin He , Xiuyuan Ou , Xiaolu Tang , Yan Liu , Xing Lu , Pei Li , Zhixia Mu , Siwen Dong , Yahan Chen , Lin Tan , Mengmeng Cao , Pinghuang Liu , Terrence Tsz-Tai Yuen , Jian Lu , Zhaohui Qian

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引用次数: 0

摘要

SARS-CoV-2不仅感染人类，也感染动物，构成反向人畜共患风险。随着SARS-CoV-2的快速演变，新冠病毒已在全球占据主导地位。在这项研究中，我们利用假病毒测定了XBB.1.16、EG.5.1、BA.2.86和jn1对27种不同动物血管紧张素转换酶2 （ACE2）同源物的易感性，发现jn1与除EG.5.1外的其他变异相比，具有显著更高的总体反向人畜共患风险潜力。活病毒感染实验进一步证实了JN.1比BA.2.86具有更高的传染性。机制分析表明，L455S可能通过降低S蛋白的热稳定性而显著提高了整体融合性和感染性。此外，我们还发现L455S突变增强了SARS-CoV-2的免疫逃避，XBB突破感染增加了针对JN.1的中和抗体水平。总之，我们的发现对冠状病毒的进入、宿主范围、进化和免疫原性提供了更好的机制理解，并强调了监测易感宿主以预防潜在疫情的重要性。

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Enhanced reverse zoonotic potential and immune evasion by omicron JN.1 variant

SARS-CoV-2 infects not only humans but also animals, posing reverse zoonotic risks. As SARS-CoV-2 rapidly evolves, JN.1 has become dominant globally. In this study, we determined the susceptibility of XBB.1.16, EG.5.1, BA.2.86, and JN.1 to 27 different animal angiotensin-converting enzyme 2 (ACE2) orthologs using pseudoviruses, and found that JN.1 displayed substantially higher overall reverse zoonotic risk potential compared to other variants except for EG.5.1. Live virus infection experiments further confirmed higher infectivity of JN.1 than BA.2.86. Mechanistic analyses revealed that L455S might be responsible for substantial increase in overall fusogenecity and infectivity by lowering S protein thermostability. Additionally, we also found that L455S mutation enhanced immune evasion of SARS-CoV-2, and XBB breakthrough infection increased levels of neutralization antibodies against JN.1. Together, our findings offer a better mechanistic understanding of CoV entry, host range, evolution, and immunogenicity and highlight the importance of surveillance of susceptible hosts to prevent potential outbreaks.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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