tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2020 Jun 30;1-36.
doi: 10.1080/22221751.2020.1787797. Online ahead of print.
Bat SARS-Like WIV1 Coronavirus Uses the ACE2 of Multiple Animal Species as Receptor and Evades IFITM3 Restriction via TMPRSS2 Activation of Membrane Fusion
Mei Zheng[SUP] 1 2 [/SUP], Xuesen Zhao[SUP] 1 2 [/SUP], Shuangli Zheng[SUP] 1 2 [/SUP], Danying Chen[SUP] 1 2 [/SUP], Pengcheng Du[SUP] 1 2 [/SUP], Xinglin Li[SUP] 1 2 [/SUP], Dong Jiang[SUP] 1 2 [/SUP], Ju-Tao Guo[SUP] 3 [/SUP], Hui Zeng[SUP] 1 2 [/SUP], Hanxin Lin[SUP] 4 [/SUP]
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Abstract
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. The efficiency of human ACE2 to support WIV1 infectious entry is similar to that of mild SARS-CoV isolate GD03 and two civet cat SL-CoVs, but approximately 50% of that to SARS-CoV Tor2. 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 activate spike-mediated membrane fusion and partially evade the IFITM3 restriction. Interestingly, we also found that amphotericin B, an antimycotic drug commonly used in clinic for patients with severe fungal infections, 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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Keywords: ACE2 receptor; IFITM; SARS-like coronavirus WIV1; TMPRSS2; viral entry.
. 2020 Jun 30;1-36.
doi: 10.1080/22221751.2020.1787797. Online ahead of print.
Bat SARS-Like WIV1 Coronavirus Uses the ACE2 of Multiple Animal Species as Receptor and Evades IFITM3 Restriction via TMPRSS2 Activation of Membrane Fusion
Mei Zheng[SUP] 1 2 [/SUP], Xuesen Zhao[SUP] 1 2 [/SUP], Shuangli Zheng[SUP] 1 2 [/SUP], Danying Chen[SUP] 1 2 [/SUP], Pengcheng Du[SUP] 1 2 [/SUP], Xinglin Li[SUP] 1 2 [/SUP], Dong Jiang[SUP] 1 2 [/SUP], Ju-Tao Guo[SUP] 3 [/SUP], Hui Zeng[SUP] 1 2 [/SUP], Hanxin Lin[SUP] 4 [/SUP]
AffiliationsExpand
- PMID: 32602823
- DOI: 10.1080/22221751.2020.1787797
Abstract
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. The efficiency of human ACE2 to support WIV1 infectious entry is similar to that of mild SARS-CoV isolate GD03 and two civet cat SL-CoVs, but approximately 50% of that to SARS-CoV Tor2. 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 activate spike-mediated membrane fusion and partially evade the IFITM3 restriction. Interestingly, we also found that amphotericin B, an antimycotic drug commonly used in clinic for patients with severe fungal infections, 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 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Keywords: ACE2 receptor; IFITM; SARS-like coronavirus WIV1; TMPRSS2; viral entry.