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IPEC-J2 Autophagy Induced by TLR4 and NSP6 Interactions Facilitate Porcine Epidemic Diarrhea Virus Replication.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • Subject Terms:
      Porcine epidemic diarrhea virus*/physiology ; Autophagy* ; Virus Replication* ; Toll-Like Receptor 4*/metabolism ; Toll-Like Receptor 4*/genetics; Animals ; Swine ; Cell Line ; Coronavirus Infections/virology ; Coronavirus Infections/veterinary ; Coronavirus Infections/metabolism ; Viral Nonstructural Proteins/metabolism ; Viral Nonstructural Proteins/genetics ; Signal Transduction ; Swine Diseases/virology ; Swine Diseases/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Host-Pathogen Interactions ; Epithelial Cells/virology
    • Abstract:
      Autophagy is an important cellular response against intracellular pathogens. However, some viruses have evolved mechanisms to hijack this defensive process to provide favorable conditions for virus replication in host cells. The porcine epidemic diarrhea virus (PEDV) has been shown to alter autophagy pathways; however, it is still unknown through which receptors PEDV induces autophagy in IPEC-J2 cells, whether autophagy facilitates PEDV replication, and which functional domains of PEDV proteins are primarily responsible for inducing autophagy. Here, we found that PEDV infection induces autophagy in host cells via distinct and uncoupled molecular pathways. RNA-seq technology was used to analyze the expression patterns of intracellular genes in PEDV-infected IPEC-J2 cells using transcriptomics. The results demonstrate that PEDV triggers autophagy via the cellular pathogen receptor TLR4 and the AKT-mTOR pathway. As evidenced by autophagosome detection, PEDV infection increases autophagosomes and light chain 3 (LC3)-II as well as downregulated AKT-mTOR phosphorylation. Our study revealed that the binding of the viral protein NSP61-2C (56-151aa) to TLR4 triggers autophagy and inactivates the AKT-mTOR pathway, both of which are critical for facilitating PEDV infection. Through screening and analysis, TLR4 was found to be a key gene involved in PEDV-induced autophagy. The screening of the key functional domains of NSP6 (56-151aa) for their ability to induce autophagy in IPEC-J2 cells provided a basis for the in-depth analysis of the pathogenic mechanism of PEDV infection-induced autophagy and promotion of self-replication and also provided an important target for the study of PEDV antiviral drugs. In conclusion, we elucidated that the PEDV infection of IPEC-J2 cells could induce autophagy and found that PEDV could use autophagy to promote its own replication.
    • References:
      Nat Cell Biol. 2011 Feb;13(2):132-41. (PMID: 21258367)
      Emerg Infect Dis. 2014 Apr;20(4):662-5. (PMID: 24795932)
      Vet Rec. 1977 Mar 19;100(12):243-4. (PMID: 888300)
      Cell Res. 2021 Jan;31(1):62-79. (PMID: 32612200)
      Emerg Infect Dis. 2014 Oct;20(10):1620-8. (PMID: 25279722)
      Autophagy. 2020 Dec;16(12):2131-2139. (PMID: 32964796)
      J Virol. 2020 Jul 16;94(15):. (PMID: 32404529)
      Cytokine. 2021 Aug;144:155581. (PMID: 34029942)
      Virulence. 2018;9(1):1176-1194. (PMID: 30067475)
      Annu Rev Genet. 2009;43:67-93. (PMID: 19653858)
      Autophagy. 2015;11(3):503-15. (PMID: 25714412)
      Front Vet Sci. 2021 Sep 10;8:744276. (PMID: 34568481)
      Cell. 2019 Jan 10;176(1-2):11-42. (PMID: 30633901)
      Virus Res. 2013 Jan;171(1):44-53. (PMID: 23108045)
      Cell Death Differ. 2009 Jan;16(1):57-69. (PMID: 18772897)
      Genes Cells. 2011 Feb;16(2):141-51. (PMID: 21210909)
      Virus Res. 2020 Sep;286:198045. (PMID: 32502552)
      Cell. 2008 Jan 11;132(1):27-42. (PMID: 18191218)
      Vet Microbiol. 2020 May;244:108684. (PMID: 32402351)
      Virus Genes. 2012 Apr;44(2):167-75. (PMID: 22270324)
      Front Immunol. 2014 Sep 25;5:461. (PMID: 25309543)
      Viruses. 2011 Aug;3(8):1332-41. (PMID: 21994782)
      PLoS Pathog. 2020 Jul 30;16(7):e1008682. (PMID: 32730327)
      Antiviral Res. 2017 Oct;146:86-95. (PMID: 28842266)
      Int J Mol Med. 2017 Jul;40(1):182-192. (PMID: 28560385)
      Autophagy. 2018;14(2):336-346. (PMID: 29166823)
      J Infect. 2020 Jul;81(1):e24-e27. (PMID: 32283146)
      Nat Rev Immunol. 2013 Oct;13(10):722-37. (PMID: 24064518)
      Nat Cell Biol. 2010 Sep;12(9):823-30. (PMID: 20811354)
      Front Immunol. 2019 Aug 06;10:1853. (PMID: 31447851)
      Autophagy. 2016;12(1):1-222. (PMID: 26799652)
      Autophagy. 2020 May;16(5):842-861. (PMID: 31318632)
      Res Vet Sci. 2018 Aug;119:99-108. (PMID: 29909130)
      Front Microbiol. 2018 Feb 15;9:210. (PMID: 29497407)
      J Virol Methods. 2005 Sep;128(1-2):192-7. (PMID: 15955576)
      Cell. 2005 Jan 28;120(2):159-62. (PMID: 15680321)
      Front Cell Dev Biol. 2021 Oct 15;9:766142. (PMID: 34722550)
      Nat Rev Microbiol. 2018 Jun;16(6):341-354. (PMID: 29556036)
      Autophagy. 2011 Nov;7(11):1335-47. (PMID: 21799305)
      Autophagy. 2014 Aug;10(8):1426-41. (PMID: 24991833)
      Protein Cell. 2018 Feb;9(2):145-151. (PMID: 28434145)
      J Steroid Biochem Mol Biol. 2019 Nov;194:105439. (PMID: 31362062)
      Vet Microbiol. 2019 Apr;231:120-128. (PMID: 30955799)
      Nature. 2011 Jan 20;469(7330):323-35. (PMID: 21248839)
      Arch Virol. 2018 Mar;163(3):623-632. (PMID: 29177545)
      Front Cell Infect Microbiol. 2021 Oct 22;11:766590. (PMID: 34746034)
      Cell Host Microbe. 2010 Nov 18;8(5):422-32. (PMID: 21075353)
      Cell Host Microbe. 2009 Oct 22;6(4):354-66. (PMID: 19837375)
      Basic Clin Pharmacol Toxicol. 2021 Feb;128(2):241-255. (PMID: 32955161)
      Vaccine. 2009 Mar 23;27(14):2030-6. (PMID: 19428826)
      Front Microbiol. 2018 Feb 23;9:301. (PMID: 29527199)
      Immune Netw. 2021 Oct 26;21(5):e37. (PMID: 34796041)
      Autophagy. 2018;14(8):1435-1455. (PMID: 29940786)
      Viruses. 2017 Mar 19;9(3):. (PMID: 28335505)
      Transl Oncol. 2022 Jan;15(1):101250. (PMID: 34688043)
      Autophagy. 2013 Apr;9(4):496-509. (PMID: 23328491)
    • Grant Information:
      U22A20527 National Natural Science Foundation Joint Fund project; LH2021C041 Natural Science Foundation of Heilongjiang Province
    • Contributed Indexing:
      Keywords: AKT-mTOR; IPEC-J2; PEDV NSP6; TLR4; autophagy; replication
    • Accession Number:
      0 (Toll-Like Receptor 4)
      0 (Viral Nonstructural Proteins)
      EC 2.7.11.1 (TOR Serine-Threonine Kinases)
    • Publication Date:
      Date Created: 20241127 Date Completed: 20241127 Latest Revision: 20241130
    • Publication Date:
      20241202
    • Accession Number:
      PMC11598845
    • Accession Number:
      10.3390/v16111787
    • Accession Number:
      39599901