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Jan 29, 2024;12

Ebola virus sequesters IRF3 in viral inclusion bodies to evade host antiviral immunity.

Lin Zhu, Jing Jin, Tingting Wang, Yong Hu, Hainan Liu, Ting Gao, Qincai Dong, Yanwen Jin, Ping Li, Zijing Liu, Yi Huang, Xuan Liu, Cheng Cao
Author Information
  1. Lin Zhu: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China. ORCID
  2. Jing Jin: Institute of Physical Science and Information Technology, Anhui University, Hefei, China.
  3. Tingting Wang: Institute of Physical Science and Information Technology, Anhui University, Hefei, China.
  4. Yong Hu: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China.
  5. Hainan Liu: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China.
  6. Ting Gao: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China.
  7. Qincai Dong: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China.
  8. Yanwen Jin: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China.
  9. Ping Li: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China.
  10. Zijing Liu: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China.
  11. Yi Huang: Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China. ORCID
  12. Xuan Liu: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China.
  13. Cheng Cao: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing, China.
PMID: 38285487 DOI: 10.7554/eLife.88122

Abstract

Viral inclusion bodies (IBs) commonly form during the replication of Ebola virus (EBOV) in infected cells, but their role in viral immune evasion has rarely been explored. Here, we found that interferon regulatory factor 3 (IRF3), but not TANK-binding kinase 1 (TBK1) or IκB kinase epsilon (IKKε), was recruited and sequestered in viral IBs when the cells were infected by EBOV transcription- and replication-competent virus-like particles (trVLPs). Nucleoprotein/virion protein 35 (VP35)-induced IBs formation was critical for IRF3 recruitment and sequestration, probably through interaction with STING. Consequently, the association of TBK1 and IRF3, which plays a vital role in type I interferon (IFN-I) induction, was blocked by EBOV trVLPs infection. Additionally, IRF3 phosphorylation and nuclear translocation induced by Sendai virus or poly(I:C) stimulation were suppressed by EBOV trVLPs. Furthermore, downregulation of STING significantly attenuated VP35-induced IRF3 accumulation in IBs. Coexpression of the viral proteins by which IB-like structures formed was much more potent in antagonizing IFN-I than expression of the IFN-I antagonist VP35 alone. These results suggested a novel immune evasion mechanism by which EBOV evades host innate immunity.

Keywords

Ebola virus VP24 VP35 immunology infectious disease inflammation microbiology virus inclusion bodies virus infection viruses

References

  1. Cell. 2014 Oct 23;159(3):477-86 [PMID: 25417101]
  2. J Virol. 2011 Mar;85(6):2512-23 [PMID: 21228243]
  3. Adv Exp Med Biol. 2021;1313:15-22 [PMID: 34661889]
  4. Nat Rev Microbiol. 2015 Nov;13(11):663-76 [PMID: 26439085]
  5. Science. 2015 Mar 13;347(6227):aaa2630 [PMID: 25636800]
  6. Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16544-9 [PMID: 24052526]
  7. J Virol. 2003 Jul;77(14):7945-56 [PMID: 12829834]
  8. J Virol. 2009 Apr;83(7):3069-77 [PMID: 19153231]
  9. J Microbiol Biotechnol. 2021 Feb 28;31(2):226-232 [PMID: 33397830]
  10. J Virol. 2014 Mar;88(6):3067-76 [PMID: 24335286]
  11. PLoS Negl Trop Dis. 2016 Jan 11;10(1):e0004364 [PMID: 26752302]
  12. Virology. 2005 Oct 25;341(2):179-89 [PMID: 16095644]
  13. J Virol. 2007 Apr;81(7):3554-62 [PMID: 17229682]
  14. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12289-94 [PMID: 11027311]
  15. PLoS Pathog. 2007 Jun;3(6):e86 [PMID: 17590081]
  16. Nat Immunol. 2003 May;4(5):491-6 [PMID: 12692549]
  17. J Vis Exp. 2014 Sep 27;(91):52381 [PMID: 25285674]
  18. J Virol. 2006 Jun;80(11):5168-78 [PMID: 16698997]
  19. Viral Immunol. 2015 Feb;28(1):10-8 [PMID: 25396298]
  20. Biochem Biophys Res Commun. 2020 Jan 15;521(3):687-692 [PMID: 31694758]
  21. Sci Rep. 2013;3:1206 [PMID: 23383374]
  22. J Immunol. 2019 Feb 1;202(3):841-856 [PMID: 30598516]
  23. J Virol. 2015 Apr;89(8):4227-36 [PMID: 25631085]
  24. PLoS Pathog. 2022 May 9;18(5):e1010532 [PMID: 35533195]
  25. J Biol Chem. 2003 Aug 8;278(32):29667-75 [PMID: 12777400]
  26. DNA Cell Biol. 2017 Apr;36(4):243-248 [PMID: 28177658]
  27. J Virol. 2006 Jun;80(11):5156-67 [PMID: 16698996]
  28. Nat Commun. 2022 Apr 26;13(1):2256 [PMID: 35474062]
  29. Nat Rev Immunol. 2003 Aug;3(8):677-85 [PMID: 12974482]
  30. Lancet Infect Dis. 2004 Aug;4(8):487-98 [PMID: 15288821]
  31. Methods. 2001 Dec;25(4):402-8 [PMID: 11846609]
  32. J Mol Cell Biol. 2014 Aug;6(4):324-37 [PMID: 24706939]
  33. J Virol. 2014 Nov;88(21):12500-10 [PMID: 25142601]
  34. PLoS Negl Trop Dis. 2018 May 3;12(5):e0006349 [PMID: 29723187]
  35. J Infect Dis. 2011 Nov;204 Suppl 3:S878-83 [PMID: 21987764]
  36. J Virol. 2012 Nov;86(21):11779-88 [PMID: 22915810]
  37. Virology. 2015 May;479-480:122-30 [PMID: 25843618]

Grants

  1. 82372255/National Natural Science Foundation of China
  2. 2022ACCP-MS04/Advanced Customer Cultivation Project of the Wuhan National Biosafety Laboratory, the Chinese Academy of Sciences
  3. 2018ZX09711003-005-005/National Major Science and Technology Projects of China
  4. 2022YFC2600704/National Major Science and Technology Projects of China

MeSH Term

Humans
Ebolavirus
Hemorrhagic Fever, Ebola
Inclusion Bodies, Viral
Interferon Regulatory Factor-3
Interferon Type I
Immune Evasion

Chemicals

Interferon Regulatory Factor-3
Interferon Type I
IRF3 protein, human
Journal Article
Article has an altmetric score of 1

Word Cloud

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