MAVS mediates a protective immune response in the brain to Rift Valley fever virus.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
23
12
2021
accepted:
25
04
2022
revised:
31
05
2022
pubmed:
19
5
2022
medline:
3
6
2022
entrez:
18
5
2022
Statut:
epublish
Résumé
Rift Valley fever virus (RVFV) is a highly pathogenic mosquito-borne virus capable of causing hepatitis, encephalitis, blindness, hemorrhagic syndrome, and death in humans and livestock. Upon aerosol infection with RVFV, the brain is a major site of viral replication and tissue damage, yet pathogenesis in this organ has been understudied. Here, we investigated the immune response in the brain of RVFV infected mice. In response to infection, microglia initiated robust transcriptional upregulation of antiviral immune genes, as well as increased levels of activation markers and cytokine secretion that is dependent on mitochondrial antiviral-signaling protein (MAVS) and independent of toll-like receptors 3 and 7. In vivo, Mavs-/- mice displayed enhanced susceptibility to RVFV as determined by increased brain viral burden and higher mortality. Single-cell RNA sequence analysis identified defects in type I interferon and interferon responsive gene expression within microglia in Mavs-/- mice, as well as dysregulated lymphocyte infiltration. The results of this study provide a crucial step towards understanding the precise molecular mechanisms by which RVFV infection is controlled in the brain and will help inform the development of vaccines and antiviral therapies that are effective in preventing encephalitis.
Identifiants
pubmed: 35584192
doi: 10.1371/journal.ppat.1010231
pii: PPATHOGENS-D-21-02593
pmc: PMC9154093
doi:
Substances chimiques
Antiviral Agents
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1010231Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Front Immunol. 2018 Apr 20;9:763
pubmed: 29731751
J Virol. 2016 Jul 27;90(16):7098-7108
pubmed: 27226371
Front Cell Neurosci. 2018 Nov 20;12:433
pubmed: 30524242
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
J Virol. 2008 Nov;82(21):10349-58
pubmed: 18715906
J Virol. 2016 Jul 27;90(16):7084-7097
pubmed: 27226375
Front Neurosci. 2019 Sep 03;13:916
pubmed: 31551681
Nature. 2018 Feb 22;554(7693):475-480
pubmed: 29443965
PLoS Negl Trop Dis. 2015 Mar 12;9(3):e0003548
pubmed: 25764399
Glia. 2002 Mar 1;37(3):258-67
pubmed: 11857684
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
PLoS One. 2017 Feb 24;12(2):e0172625
pubmed: 28235099
Am J Trop Med Hyg. 2010 Aug;83(2 Suppl):14-21
pubmed: 20682901
J Infect. 2012 Jul;65(1):1-16
pubmed: 22484271
J Neuroimmunol. 2002 Sep;130(1-2):22-31
pubmed: 12225885
J Virol. 2012 Dec;86(23):12954-70
pubmed: 22993156
Immunity. 2019 Jan 15;50(1):253-271.e6
pubmed: 30471926
Nat Protoc. 2007;2(6):1490-8
pubmed: 17545985
J Neuroinflammation. 2019 Jan 31;16(1):22
pubmed: 30704498
Trends Immunol. 2014 Feb;35(2):79-87
pubmed: 24316012
Nat Immunol. 2016 Jul;17(7):797-805
pubmed: 27135602
Cancers (Basel). 2020 Mar 14;12(3):
pubmed: 32183351
Sci Immunol. 2020 Jun 5;5(48):
pubmed: 32503876
Nat Immunol. 2011 Jun 05;12(7):624-30
pubmed: 21642987
Immunity. 2009 Feb 20;30(2):242-53
pubmed: 19200759
Proc Natl Acad Sci U S A. 2017 Jan 3;114(1):E95-E104
pubmed: 27980033
J Immunol. 2001 Feb 15;166(4):2260-9
pubmed: 11160280
PLoS Negl Trop Dis. 2013 Apr 04;7(4):e2156
pubmed: 23593523
Emerg Microbes Infect. 2013 Dec;2(12):e81
pubmed: 26038446
Cell Rep. 2012 Apr 19;1(4):334-340
pubmed: 22832225
J Immunother Cancer. 2019 Jul 5;7(1):168
pubmed: 31277710
Virology. 2012 Sep 15-30;431(1-2):58-70
pubmed: 22687428
Science. 2021 Oct 29;374(6567):548
pubmed: 34709902
Nat Rev Immunol. 2015 Jun;15(6):388-400
pubmed: 25998963
PLoS Negl Trop Dis. 2014 Jun 12;8(6):e2874
pubmed: 24922480
Virology. 2010 Nov 25;407(2):256-67
pubmed: 20850165
PLoS Pathog. 2019 Jun 20;15(6):e1007833
pubmed: 31220182
Neuron. 2013 Apr 24;78(2):214-32
pubmed: 23622060
Clin Infect Dis. 2003 Oct 15;37(8):1084-92
pubmed: 14523773
Neurobiol Dis. 2010 Mar;37(3):510-8
pubmed: 19913097
PLoS Pathog. 2010 Feb 05;6(2):e1000757
pubmed: 20140199
Viruses. 2021 Jan 23;13(2):
pubmed: 33498715
PLoS Negl Trop Dis. 2015 Mar 10;9(3):e0003584
pubmed: 25756647
Cell. 2018 Jan 25;172(3):500-516.e16
pubmed: 29275859
Ann Clin Microbiol Antimicrob. 2020 Jan 22;19(1):4
pubmed: 31969141
Front Immunol. 2021 Mar 19;12:645850
pubmed: 33815404
Cell Rep. 2018 Oct 2;25(1):118-129.e4
pubmed: 30282022
Fed Regist. ;82(12):6278-94
pubmed: 28106357
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
J Virol. 2015 Dec 23;90(5):2600-15
pubmed: 26699642
Glia. 2017 Sep;65(9):1504-1520
pubmed: 28618077
J Clin Microbiol. 2007 Nov;45(11):3506-13
pubmed: 17804663
Sci Rep. 2016 Jun 09;6:27670
pubmed: 27279150
Nat Immunol. 2013 Apr;14(4):346-55
pubmed: 23416614
J Virol. 2018 Nov 27;92(24):
pubmed: 30258000
Cell Rep. 2017 Dec 12;21(11):3271-3284
pubmed: 29241552
Front Cell Neurosci. 2021 Nov 24;15:749587
pubmed: 34899188
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Int J Mol Sci. 2020 Jul 28;21(15):
pubmed: 32731618
Eur J Immunol. 2015 Jan;45(1):192-202
pubmed: 25308526
Biomolecules. 2021 Jul 26;11(8):
pubmed: 34439764
Curr Opin Neurol. 2020 Jun;33(3):405-412
pubmed: 32304440
Vet Res. 2010 Nov-Dec;41(6):61
pubmed: 21188836
J Virol. 2013 May;87(9):4846-60
pubmed: 23408632
J Virol. 2006 Jan;80(1):119-29
pubmed: 16352536
Nat Biotechnol. 2014 Sep;32(9):896-902
pubmed: 25150836
Front Immunol. 2021 Sep 09;12:621090
pubmed: 34566948
J Virol. 2013 Jun;87(11):6161-71
pubmed: 23536675
Glia. 2020 Nov;68(11):2345-2360
pubmed: 32449994
J Vis Exp. 2017 Jun 22;(124):
pubmed: 28671658
J Gen Virol. 2015 Jul;96(Pt 7):1651-1663
pubmed: 25759029
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11
pubmed: 19465376
J Pharmacol Sci. 2015 Aug;128(4):216-20
pubmed: 26318672