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SARS-CoV-2 nucleocapsid protein impairs stress granule formation to promote viral replication.
Zheng, Zhou-Qin; Wang, Su-Yun; Xu, Zhi-Sheng; Fu, Yu-Zhi; Wang, Yan-Yi.
  • Zheng ZQ; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Wang SY; University of Chinese Academy of Sciences, Beijing, China.
  • Xu ZS; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Fu YZ; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Wang YY; Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China. yuzhi.fu@wh.iov.cn.
Cell Discov ; 7(1): 38, 2021 May 25.
Article in English | MEDLINE | ID: covidwho-1243287
Semantic information from SemMedBD (by NLM)
1. Measles Virus Nucleoprotein PART_OF 2019 novel coronavirus
Subject
Measles Virus Nucleoprotein
Predicate
PART_OF
Object
2019 novel coronavirus
2. Measles Virus Nucleoprotein DISRUPTS P-body
Subject
Measles Virus Nucleoprotein
Predicate
DISRUPTS
Object
P-body
3. Lung LOCATION_OF Severe disease
Subject
Lung
Predicate
LOCATION_OF
Object
Severe disease
4. RN AUGMENTS C1325596
Subject
RN
Predicate
AUGMENTS
Object
C1325596
5. eIF-2 Kinase|PKLR|EIF2AK2 COEXISTS_WITH Measles Virus Nucleoprotein
Subject
eIF-2 Kinase|PKLR|EIF2AK2
Predicate
COEXISTS_WITH
Object
Measles Virus Nucleoprotein
6. RN STIMULATES C3710914|5610
Subject
RN
Predicate
STIMULATES
Object
C3710914|5610
7. Measles Virus Nucleoprotein INTERACTS_WITH G3BP1 gene|G3BP1
Subject
Measles Virus Nucleoprotein
Predicate
INTERACTS_WITH
Object
G3BP1 gene|G3BP1
8. G3BP1 gene|G3BP1 AFFECTS Anabolism
Subject
G3BP1 gene|G3BP1
Predicate
AFFECTS
Object
Anabolism
9. G3BP1 gene|G3BP1 DISRUPTS P-body
Subject
G3BP1 gene|G3BP1
Predicate
DISRUPTS
Object
P-body
10. EIF2AK2 protei DISRUPTS C1325596
Subject
EIF2AK2 protei
Predicate
DISRUPTS
Object
C1325596
11. Measles Virus Nucleoprotein PART_OF SARS coronavirus
Subject
Measles Virus Nucleoprotein
Predicate
PART_OF
Object
SARS coronavirus
12. Measles Virus Nucleoprotein INTERACTS_WITH EIF2AK2 protei
Subject
Measles Virus Nucleoprotein
Predicate
INTERACTS_WITH
Object
EIF2AK2 protei
13. Measles Virus Nucleoprotein PART_OF Middle East Respiratory Syndrome Coronavirus
Subject
Measles Virus Nucleoprotein
Predicate
PART_OF
Object
Middle East Respiratory Syndrome Coronavirus
14. Measles Virus Nucleoprotein NEG_INTERACTS_WITH G3BP1 gene|G3BP1
Subject
Measles Virus Nucleoprotein
Predicate
NEG_INTERACTS_WITH
Object
G3BP1 gene|G3BP1
15. Betacoronavirus PROCESS_OF Homo sapiens
Subject
Betacoronavirus
Predicate
PROCESS_OF
Object
Homo sapiens
16. Measles Virus Nucleoprotein AUGMENTS Virus Replication
Subject
Measles Virus Nucleoprotein
Predicate
AUGMENTS
Object
Virus Replication
17. Measles Virus Nucleoprotein PART_OF 2019 novel coronavirus
Subject
Measles Virus Nucleoprotein
Predicate
PART_OF
Object
2019 novel coronavirus
18. Measles Virus Nucleoprotein DISRUPTS P-body
Subject
Measles Virus Nucleoprotein
Predicate
DISRUPTS
Object
P-body
19. Lung LOCATION_OF Severe disease
Subject
Lung
Predicate
LOCATION_OF
Object
Severe disease
20. RNA, Viral AUGMENTS P-body
Subject
RNA, Viral
Predicate
AUGMENTS
Object
P-body
21. eIF-2 Kinase|PKLR|EIF2AK2 COEXISTS_WITH Measles Virus Nucleoprotein
Subject
eIF-2 Kinase|PKLR|EIF2AK2
Predicate
COEXISTS_WITH
Object
Measles Virus Nucleoprotein
22. RNA, Double-Stranded STIMULATES EIF2AK2 protein, human|EIF2AK2
Subject
RNA, Double-Stranded
Predicate
STIMULATES
Object
EIF2AK2 protein, human|EIF2AK2
23. Measles Virus Nucleoprotein INTERACTS_WITH G3BP1 gene|G3BP1
Subject
Measles Virus Nucleoprotein
Predicate
INTERACTS_WITH
Object
G3BP1 gene|G3BP1
24. G3BP1 gene|G3BP1 AFFECTS Anabolism
Subject
G3BP1 gene|G3BP1
Predicate
AFFECTS
Object
Anabolism
25. G3BP1 gene|G3BP1 DISRUPTS P-body
Subject
G3BP1 gene|G3BP1
Predicate
DISRUPTS
Object
P-body
26. EIF2AK2 protein, human|EIF2AK2 DISRUPTS P-body
Subject
EIF2AK2 protein, human|EIF2AK2
Predicate
DISRUPTS
Object
P-body
27. Measles Virus Nucleoprotein PART_OF SARS coronavirus
Subject
Measles Virus Nucleoprotein
Predicate
PART_OF
Object
SARS coronavirus
28. Measles Virus Nucleoprotein INTERACTS_WITH EIF2AK2 protein, human|EIF2AK2
Subject
Measles Virus Nucleoprotein
Predicate
INTERACTS_WITH
Object
EIF2AK2 protein, human|EIF2AK2
29. RNA, Double-Stranded AUGMENTS P-body
Subject
RNA, Double-Stranded
Predicate
AUGMENTS
Object
P-body
30. Measles Virus Nucleoprotein PART_OF Middle East Respiratory Syndrome Coronavirus
Subject
Measles Virus Nucleoprotein
Predicate
PART_OF
Object
Middle East Respiratory Syndrome Coronavirus
31. Measles Virus Nucleoprotein NEG_INTERACTS_WITH G3BP1 gene|G3BP1
Subject
Measles Virus Nucleoprotein
Predicate
NEG_INTERACTS_WITH
Object
G3BP1 gene|G3BP1
32. Betacoronavirus PROCESS_OF Homo sapiens
Subject
Betacoronavirus
Predicate
PROCESS_OF
Object
Homo sapiens
33. Measles Virus Nucleoprotein AUGMENTS Virus Replication
Subject
Measles Virus Nucleoprotein
Predicate
AUGMENTS
Object
Virus Replication
ABSTRACT
The newly emerging coronavirus SARS-CoV-2 causes severe lung disease and substantial mortality. How the virus evades host defense for efficient replication is not fully understood. In this report, we found that the SARS-CoV-2 nucleocapsid protein (NP) impaired stress granule (SG) formation induced by viral RNA. SARS-CoV-2 NP associated with the protein kinase PKR after dsRNA stimulation. SARS-CoV-2 NP did not affect dsRNA-induced PKR oligomerization, but impaired dsRNA-induced PKR phosphorylation (a hallmark of its activation) as well as SG formation. SARS-CoV-2 NP also targeted the SG-nucleating protein G3BP1 and impaired G3BP1-mediated SG formation. Deficiency of PKR or G3BP1 impaired dsRNA-triggered SG formation and increased SARS-CoV-2 replication. The NP of SARS-CoV also targeted both PKR and G3BP1 to impair dsRNA-induced SG formation, whereas the NP of MERS-CoV targeted PKR, but not G3BP1 for the impairment. Our findings suggest that SARS-CoV-2 NP promotes viral replication by impairing formation of antiviral SGs, and reveal a conserved mechanism on evasion of host antiviral responses by highly pathogenic human betacoronaviruses.

Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Cell Discov Year: 2021 Document Type: Article Affiliation country: S41421-021-00275-0

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: Cell Discov Year: 2021 Document Type: Article Affiliation country: S41421-021-00275-0