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The interferon-stimulated exosomal hACE2 potently inhibits SARS-CoV-2 replication through competitively blocking the virus entry.
Zhang, Junsong; Huang, Feng; Xia, Baijin; Yuan, Yaochang; Yu, Fei; Wang, Guanwen; Chen, Qianyu; Wang, Qian; Li, Yuzhuang; Li, Rong; Song, Zheng; Pan, Ting; Chen, Jingliang; Lu, Gen; Zhang, Hui.
  • Zhang J; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Huang F; 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.
  • Xia B; 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.
  • Yuan Y; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong, China.
  • Yu F; 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.
  • Wang G; 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.
  • Chen Q; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Wang Q; 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.
  • Li Y; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Li R; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Song Z; Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Pan T; 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.
  • Chen J; 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.
  • Lu G; 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.
  • Zhang H; 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.
Signal Transduct Target Ther ; 6(1): 189, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1226420
Semantic information from SemMedBD (by NLM)
1. Interferons STIMULATES angiotensin converting enzyme 2
Subject
Interferons
Predicate
STIMULATES
Object
angiotensin converting enzyme 2
2. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
3. Vitronecti PART_OF C5203676
Subject
Vitronecti
Predicate
PART_OF
Object
C5203676
4. Cells PRODUCES angiotensin converting enzyme 2
Subject
Cells
Predicate
PRODUCES
Object
angiotensin converting enzyme 2
5. Exosomes LOCATION_OF Receptor
Subject
Exosomes
Predicate
LOCATION_OF
Object
Receptor
6. IFNA1 STIMULATES Receptor
Subject
IFNA1
Predicate
STIMULATES
Object
Receptor
7. Exosomes AFFECTS Virus Internalization
Subject
Exosomes
Predicate
AFFECTS
Object
Virus Internalization
8. Interferons STIMULATES angiotensin converting enzyme 2
Subject
Interferons
Predicate
STIMULATES
Object
angiotensin converting enzyme 2
9. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
10. Vitronectin, human PART_OF 2019 novel coronavirus
Subject
Vitronectin, human
Predicate
PART_OF
Object
2019 novel coronavirus
11. Cells PRODUCES angiotensin converting enzyme 2
Subject
Cells
Predicate
PRODUCES
Object
angiotensin converting enzyme 2
12. Exosomes LOCATION_OF Receptors, Virus
Subject
Exosomes
Predicate
LOCATION_OF
Object
Receptors, Virus
13. IFNA1 STIMULATES Receptors, Virus
Subject
IFNA1
Predicate
STIMULATES
Object
Receptors, Virus
14. Exosomes AFFECTS Virus Internalization
Subject
Exosomes
Predicate
AFFECTS
Object
Virus Internalization
ABSTRACT
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 IFNα/ß 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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Replication / Interferon-beta / Interferon-alpha / Virus Internalization / Exosomes / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00604-5

Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Replication / Interferon-beta / Interferon-alpha / Virus Internalization / Exosomes / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00604-5