PMID- 33980808
OWN - NLM
STAT- MEDLINE
DCOM- 20210531
LR  - 20210531
IS  - 2059-3635 (Electronic)
IS  - 2095-9907 (Print)
IS  - 2059-3635 (Linking)
VI  - 6
IP  - 1
DP  - 2021 May 12
TI  - The interferon-stimulated exosomal hACE2 potently inhibits SARS-CoV-2 replication 
      through competitively blocking the virus entry.
PG  - 189
LID - 10.1038/s41392-021-00604-5 [doi]
LID - 189
AB  - Since the outbreak of coronavirus disease 2019 (COVID-19), it has become a global 
      pandemic. The spike (S) protein of etiologic severe acute respiratory syndrome 
      coronavirus 2 (SARS-CoV-2) specifically recognizes human angiotensin-converting 
      enzyme 2 (hACE2) as its receptor, which is recently identified as an interferon 
      (IFN)-stimulated gene. Here, we find that hACE2 exists on the surface of exosomes 
      released by different cell types, and the expression of exosomal hACE2 is 
      increased by IFNalpha/beta treatment. In particular, exosomal hACE2 can specifically 
      block the cell entry of SARS-CoV-2, subsequently inhibit the replication of 
      SARS-CoV-2 in vitro and ex vivo. Our findings have indicated that IFN is able to 
      upregulate a viral receptor on the exosomes which competitively block the virus 
      entry, exhibiting a potential antiviral strategy.
FAU - Zhang, Junsong
AU  - Zhang J
AD  - Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 
      Guangzhou, Guangdong, China.
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
FAU - Huang, Feng
AU  - Huang F
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
AD  - Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong 
      Laboratory), Guangzhou, Guangdong, China.
FAU - Xia, Baijin
AU  - Xia B
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
FAU - Yuan, Yaochang
AU  - Yuan Y
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
FAU - Yu, Fei
AU  - Yu F
AD  - Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 
      Guangzhou, Guangdong, China.
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
FAU - Wang, Guanwen
AU  - Wang G
AD  - Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 
      Guangzhou, Guangdong, China.
FAU - Chen, Qianyu
AU  - Chen Q
AD  - Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 
      Guangzhou, Guangdong, China.
FAU - Wang, Qian
AU  - Wang Q
AD  - Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 
      Guangzhou, Guangdong, China.
FAU - Li, Yuzhuang
AU  - Li Y
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
FAU - Li, Rong
AU  - Li R
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
FAU - Song, Zheng
AU  - Song Z
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
FAU - Pan, Ting
AU  - Pan T
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
AD  - School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
FAU - Chen, Jingliang
AU  - Chen J
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China.
AD  - Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical 
      University, Guangzhou, China.
FAU - Lu, Gen
AU  - Lu G
AD  - Department of Respiratory Diseases, Guangzhou Women and Children Hospital, 
      Guangzhou, Guangdong, China.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Institute of Human Virology, Key Laboratory of Tropical Disease Control of 
      Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent 
      and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangzhou, Guangdong, China. zhangh92@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210512
PL  - England
TA  - Signal Transduct Target Ther
JT  - Signal transduction and targeted therapy
JID - 101676423
RN  - 0 (Interferon-alpha)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Angiotensin-Converting Enzyme 2/genetics/*metabolism
MH  - Animals
MH  - Chlorocebus aethiops
MH  - Exosomes/genetics/*metabolism/virology
MH  - HEK293 Cells
MH  - Humans
MH  - Interferon-alpha/*pharmacology
MH  - Interferon-beta/*pharmacology
MH  - Mice
MH  - Mice, Transgenic
MH  - SARS-CoV-2/*physiology
MH  - Vero Cells
MH  - Virus Internalization/*drug effects
MH  - Virus Replication/*drug effects
PMC - PMC8113286
COIS- The authors declare no competing interests.
EDAT- 2021/05/14 06:00
MHDA- 2021/06/01 06:00
PMCR- 2021/05/12
CRDT- 2021/05/13 05:47
PHST- 2020/09/15 00:00 [received]
PHST- 2021/03/21 00:00 [accepted]
PHST- 2021/02/25 00:00 [revised]
PHST- 2021/05/13 05:47 [entrez]
PHST- 2021/05/14 06:00 [pubmed]
PHST- 2021/06/01 06:00 [medline]
PHST- 2021/05/12 00:00 [pmc-release]
AID - 10.1038/s41392-021-00604-5 [pii]
AID - 604 [pii]
AID - 10.1038/s41392-021-00604-5 [doi]
PST - epublish
SO  - Signal Transduct Target Ther. 2021 May 12;6(1):189. doi: 
      10.1038/s41392-021-00604-5.