An atlas of sarbecovirus infectivity across diverse ACE2 orthologs.

IF 4.5 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2026-10-03 eCollection Date: 2026-10-16 DOI:10.1016/j.isci.2026.117769

Yeqing Sun, Ziqi Cheng, Xi Wu, Kefang Liu, Lin Wang, Dongchun Yang, Weijin Huang, Jianhui Nie

{"title":"An atlas of sarbecovirus infectivity across diverse ACE2 orthologs.","authors":"Yeqing Sun, Ziqi Cheng, Xi Wu, Kefang Liu, Lin Wang, Dongchun Yang, Weijin Huang, Jianhui Nie","doi":"10.1016/j.isci.2026.117769","DOIUrl":null,"url":null,"abstract":"Sarbecoviruses pose a substantial zoonotic threat, yet the determinants governing their host range remain incompletely defined. To systematically investigate host entry mechanisms, we generated a panel of vesicular stomatitis virus (VSV) pseudoviruses representing 46 sarbecoviruses and assessed their infectivity across 66 angiotensin-converting enzyme 2 (ACE2) orthologs. This analysis produced a high-resolution host-entry landscape with direct implications for cross-species transmission risk. We found that all severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) isolates, WIV1, and pangolin-derived sarbecoviruses demonstrated broad ACE2 usage, whereas no sarbecovirus utilized alternative entry factors including neuropilin-1, CD147, AXL, or TMEM106B. Notably, ACE2 orthologs from Rhinolophus affinis and Miniopterus schreibersii supported infection by nearly all clade 1 sarbecoviruses, identifying highly permissive host receptors. We also identified residues 27 and 42 of ACE2 as critical determinants of sarbecovirus host tropism. Together, these findings define host entry constraints relevant to receptor-based risk assessment and inform surveillance and pandemic preparedness.","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 10","pages":"117769"},"PeriodicalIF":4.5000,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661211/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"iScience","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.isci.2026.117769","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/10/16 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Sarbecoviruses pose a substantial zoonotic threat, yet the determinants governing their host range remain incompletely defined. To systematically investigate host entry mechanisms, we generated a panel of vesicular stomatitis virus (VSV) pseudoviruses representing 46 sarbecoviruses and assessed their infectivity across 66 angiotensin-converting enzyme 2 (ACE2) orthologs. This analysis produced a high-resolution host-entry landscape with direct implications for cross-species transmission risk. We found that all severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) isolates, WIV1, and pangolin-derived sarbecoviruses demonstrated broad ACE2 usage, whereas no sarbecovirus utilized alternative entry factors including neuropilin-1, CD147, AXL, or TMEM106B. Notably, ACE2 orthologs from Rhinolophus affinis and Miniopterus schreibersii supported infection by nearly all clade 1 sarbecoviruses, identifying highly permissive host receptors. We also identified residues 27 and 42 of ACE2 as critical determinants of sarbecovirus host tropism. Together, these findings define host entry constraints relevant to receptor-based risk assessment and inform surveillance and pandemic preparedness.

查看原文本刊更多论文

不同ACE2同源物的sarbecvirus传染性图谱。

人畜共患的Sarbecoviruses构成重大威胁,但决定因素管理他们的宿主范围仍然不完全定义。为了系统地研究宿主进入机制，我们生成了一组代表46种sarbecovirus的水泡性口炎病毒（VSV）假病毒，并评估了它们在66种血管紧张素转换酶2 （ACE2）同源物中的传染性。该分析产生了高分辨率的宿主进入景观，对跨物种传播风险具有直接影响。我们发现，所有SARS-CoV-1分离株、WIV1和穿山甲来源的sarbecovirus均广泛使用ACE2，而sarbecovirus没有使用其他进入因子，包括neuropilin-1、CD147、AXL或TMEM106B。值得注意的是，来自affinus Rhinolophus和schreiberminiopterus的ACE2同源物支持几乎所有进化支1 sarbecovirus的感染，鉴定出高度允许的宿主受体。我们还发现ACE2残基27和42是sarbecvirus宿主亲和性的关键决定因素。总之，这些发现确定了与基于受体的风险评估相关的宿主进入限制，并为监测和大流行防范提供了信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.