USP18 enhances dengue virus replication by regulating mitochondrial DNA release.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 11 2023
17 11 2023
Historique:
received:
19
07
2023
accepted:
14
11
2023
medline:
20
11
2023
pubmed:
18
11
2023
entrez:
18
11
2023
Statut:
epublish
Résumé
Dengue virus (DENV) infection remains a challenging health threat worldwide. Ubiquitin-specific protease 18 (USP18), which preserves the anti-interferon (IFN) effect, is an ideal target through which DENV mediates its own immune evasion. However, much of the function and mechanism of USP18 in regulating DENV replication remains incompletely understood. In addition, whether USP18 regulates DENV replication merely by causing IFN hyporesponsiveness is not clear. In the present study, by using several different approaches to block IFN signaling, including IFN neutralizing antibodies (Abs), anti-IFN receptor Abs, Janus kinase inhibitors and IFN alpha and beta receptor subunit 1 (IFNAR1)knockout cells, we showed that USP18 may regulate DENV replication in IFN-associated and IFN-unassociated manners. Localized in mitochondria, USP18 regulated the release of mitochondrial DNA (mtDNA) to the cytosol to affect viral replication, and mechanisms such as mitochondrial reactive oxygen species (mtROS) production, changes in mitochondrial membrane potential, mobilization of calcium into mitochondria, 8-oxoguanine DNA glycosylase 1 (OGG1) expression, oxidation and fragmentation of mtDNA, and opening of the mitochondrial permeability transition pore (mPTP) were involved in USP18-regulated mtDNA release to the cytosol. We therefore identify mitochondrial machineries that are regulated by USP18 to affect DENV replication and its association with IFN effects.
Identifiants
pubmed: 37978268
doi: 10.1038/s41598-023-47584-w
pii: 10.1038/s41598-023-47584-w
pmc: PMC10656416
doi:
Substances chimiques
DNA, Mitochondrial
0
Interferon-alpha
0
USP18 protein, human
EC 3.4.19.12
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
20126Informations de copyright
© 2023. The Author(s).
Références
Nature. 2018 Aug;560(7717):198-203
pubmed: 30046112
Cell. 2020 Oct 29;183(3):636-649.e18
pubmed: 33031745
Nat Commun. 2023 Feb 16;14(1):872
pubmed: 36797275
Nat Struct Mol Biol. 2017 Mar;24(3):279-289
pubmed: 28165510
Nature. 2021 Mar;591(7850):477-481
pubmed: 33627873
Cell Host Microbe. 2016 Sep 14;20(3):342-356
pubmed: 27545046
Cell. 2015 Jul 30;162(3):488-92
pubmed: 26232221
iScience. 2021 May 03;24(6):102498
pubmed: 34142025
Sci Signal. 2012 Jul 03;5(231):ra47
pubmed: 22763339
Front Immunol. 2022 Jul 06;13:889196
pubmed: 35874775
Mol Cell. 2021 May 6;81(9):1863-1865
pubmed: 33961775
EMBO Rep. 2020 Apr 3;21(4):e49799
pubmed: 32202065
Nat Immunol. 2011 Nov 20;13(1):51-7
pubmed: 22101728
Nat Med. 2004 Dec;10(12):1374-8
pubmed: 15531891
Antimicrob Agents Chemother. 2011 Sep;55(9):4311-9
pubmed: 21709085
Life Sci. 2007 Sep 15;81(14):1160-6
pubmed: 17870132
Science. 2018 Feb 23;359(6378):
pubmed: 29472455
Biochem Soc Trans. 2023 Feb 27;51(1):457-472
pubmed: 36815695
Cell Res. 2016 Dec;26(12):1302-1319
pubmed: 27801882
J Virol. 2021 Mar 3;95(10):
pubmed: 33658340
Gastroenterology. 2017 Aug;153(2):566-578.e5
pubmed: 28456632
PLoS Pathog. 2013 Oct;9(10):e1003650
pubmed: 24204252
EMBO J. 2014 Oct 1;33(19):2142-56
pubmed: 25107473
Sci Immunol. 2018 Sep 28;3(27):
pubmed: 30266866
Nat Med. 2016 Feb;22(2):146-53
pubmed: 26779811
Mol Cell. 2021 Sep 16;81(18):3866-3876.e2
pubmed: 34352204
Free Radic Biol Med. 2016 Jul;96:78-88
pubmed: 27091693
J Biol Chem. 2002 Mar 22;277(12):9976-81
pubmed: 11788588
Nature. 2016 Jul 06;535(7610):153-8
pubmed: 27383986
Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165761
pubmed: 32169503
J Immunol. 2005 Jun 15;174(12):8163-72
pubmed: 15944325
J Exp Med. 2013 Jul 29;210(8):1575-90
pubmed: 23825189
Nature. 2023 Mar;615(7952):499-506
pubmed: 36890229
Immunity. 2022 Aug 9;55(8):1370-1385.e8
pubmed: 35835107
Lancet Infect Dis. 2017 Mar;17(3):e70-e78
pubmed: 28185869
Front Microbiol. 2021 Apr 30;12:682380
pubmed: 34017322
Trends Immunol. 2019 Dec;40(12):1120-1133
pubmed: 31744765
Gastroenterology. 2006 Nov;131(5):1584-91
pubmed: 17101330
J Leukoc Biol. 2018 Feb 13;:
pubmed: 29437254
EMBO J. 2015 Jun 12;34(12):1612-29
pubmed: 25896511
EMBO Rep. 2018 Aug;19(8):
pubmed: 29880709
Trends Immunol. 2023 Mar;44(3):188-200
pubmed: 36739208
Trends Biochem Sci. 2021 Oct;46(10):812-821
pubmed: 34088564
Cell Mol Life Sci. 2004 Dec;61(24):3100-3
pubmed: 15583871
Hepatology. 2017 Dec;66(6):1866-1884
pubmed: 28718215
J Immunol. 2008 Nov 1;181(9):6467-72
pubmed: 18941237
NPJ Vaccines. 2023 Apr 15;8(1):55
pubmed: 37061527
Nat Commun. 2021 May 20;12(1):2970
pubmed: 34016972
J Gen Virol. 2023 Mar;104(3):
pubmed: 36857199
J Biol Chem. 2015 Jan 16;290(3):1485-95
pubmed: 25429107
Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1577-82
pubmed: 25605921
Science. 2019 Dec 20;366(6472):1531-1536
pubmed: 31857488