Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion

Diverse SARS-like coronaviruses (SL-CoVs) have been identified from bats and other animal species. Like SARS-CoV, some bat SL-CoVs, such as WIV1, also use angiotensin converting enzyme 2 (ACE2) from human and bat as entry receptor. However, whether these viruses can also use the ACE2 of other animal...

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Main Authors: Mei Zheng, Xuesen Zhao, Shuangli Zheng, Danying Chen, Pengcheng Du, Xinglin Li, Dong Jiang, Ju-Tao Guo, Hui Zeng, Hanxin Lin
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1787797
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author Mei Zheng
Xuesen Zhao
Shuangli Zheng
Danying Chen
Pengcheng Du
Xinglin Li
Dong Jiang
Ju-Tao Guo
Hui Zeng
Hanxin Lin
author_facet Mei Zheng
Xuesen Zhao
Shuangli Zheng
Danying Chen
Pengcheng Du
Xinglin Li
Dong Jiang
Ju-Tao Guo
Hui Zeng
Hanxin Lin
author_sort Mei Zheng
collection DOAJ
description Diverse SARS-like coronaviruses (SL-CoVs) have been identified from bats and other animal species. Like SARS-CoV, some bat SL-CoVs, such as WIV1, also use angiotensin converting enzyme 2 (ACE2) from human and bat as entry receptor. However, whether these viruses can also use the ACE2 of other animal species as their receptor remains to be determined. We report herein that WIV1 has a broader tropism to ACE2 orthologs than SARS-CoV isolate Tor2. Among the 9 ACE2 orthologs examined, human ACE2 exhibited the highest efficiency to mediate the infection of WIV1 pseudotyped virus. Our findings thus imply that WIV1 has the potential to infect a wide range of wild animals and may directly jump to humans. We also showed that cell entry of WIV1 could be restricted by interferon-induced transmembrane proteins (IFITMs). However, WIV1 could exploit the airway protease TMPRSS2 to partially evade the IFITM3 restriction. Interestingly, we also found that amphotericin B could enhance the infectious entry of SARS-CoVs and SL-CoVs by evading IFITM3-mediated restriction. Collectively, our findings further underscore the risk of exposure to animal SL-CoVs and highlight the vulnerability of patients who take amphotericin B to infection by SL-CoVs, including the most recently emerging (SARS-CoV-2).
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spelling doaj-art-b53a2e0ff49b4cd3a52029ee3de7e3572025-08-20T02:12:15ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01911567157910.1080/22221751.2020.1787797Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusionMei Zheng0Xuesen Zhao1Shuangli Zheng2Danying Chen3Pengcheng Du4Xinglin Li5Dong Jiang6Ju-Tao Guo7Hui Zeng8Hanxin Lin9Institute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaInstitute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaBaruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA, USAInstitute of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaDepartment of Pathology and Laboratory Medicine, Western University, London, CanadaDiverse SARS-like coronaviruses (SL-CoVs) have been identified from bats and other animal species. Like SARS-CoV, some bat SL-CoVs, such as WIV1, also use angiotensin converting enzyme 2 (ACE2) from human and bat as entry receptor. However, whether these viruses can also use the ACE2 of other animal species as their receptor remains to be determined. We report herein that WIV1 has a broader tropism to ACE2 orthologs than SARS-CoV isolate Tor2. Among the 9 ACE2 orthologs examined, human ACE2 exhibited the highest efficiency to mediate the infection of WIV1 pseudotyped virus. Our findings thus imply that WIV1 has the potential to infect a wide range of wild animals and may directly jump to humans. We also showed that cell entry of WIV1 could be restricted by interferon-induced transmembrane proteins (IFITMs). However, WIV1 could exploit the airway protease TMPRSS2 to partially evade the IFITM3 restriction. Interestingly, we also found that amphotericin B could enhance the infectious entry of SARS-CoVs and SL-CoVs by evading IFITM3-mediated restriction. Collectively, our findings further underscore the risk of exposure to animal SL-CoVs and highlight the vulnerability of patients who take amphotericin B to infection by SL-CoVs, including the most recently emerging (SARS-CoV-2).https://www.tandfonline.com/doi/10.1080/22221751.2020.1787797SARS-like coronavirus WIV1ACE2 receptorviral entryIFITMTMPRSS2
spellingShingle Mei Zheng
Xuesen Zhao
Shuangli Zheng
Danying Chen
Pengcheng Du
Xinglin Li
Dong Jiang
Ju-Tao Guo
Hui Zeng
Hanxin Lin
Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion
Emerging Microbes and Infections
SARS-like coronavirus WIV1
ACE2 receptor
viral entry
IFITM
TMPRSS2
title Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion
title_full Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion
title_fullStr Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion
title_full_unstemmed Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion
title_short Bat SARS-Like WIV1 coronavirus uses the ACE2 of multiple animal species as receptor and evades IFITM3 restriction via TMPRSS2 activation of membrane fusion
title_sort bat sars like wiv1 coronavirus uses the ace2 of multiple animal species as receptor and evades ifitm3 restriction via tmprss2 activation of membrane fusion
topic SARS-like coronavirus WIV1
ACE2 receptor
viral entry
IFITM
TMPRSS2
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1787797
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