Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I.
Caspase-12 has been shown to negatively modulate inflammasome signaling during bacterial infection. Its function in viral immunity, however, has not been characterized. We now report an important role for caspase-12 in controlling viral infection via the pattern-recognition receptor RIG-I. After challenge with West Nile virus (WNV), caspase-12-deficient mice had greater mortality, higher viral burden and defective type I interferon response compared with those of challenged wild-type mice. In vitro studies of primary neurons and mouse embryonic fibroblasts showed that caspase-12 positively modulated the production of type I interferon by regulating E3 ubiquitin ligase TRIM25-mediated ubiquitination of RIG-I, a critical signaling event for the type I interferon response to WNV and other important viral pathogens.
Wang
Penghua
P
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Arjona
Alvaro
A
Zhang
Yue
Y
Sultana
Hameeda
H
Dai
Jianfeng
J
Yang
Long
L
LeBlanc
Philippe M
PM
Doiron
Karine
K
Saleh
Maya
M
Fikrig
Erol
E
D000818:Animals; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D014901:West Nile Fever / Q000235:genetics / Q000276:immunology*; D014902:West Nile virus
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D011991:Receptors, Virus; D014157:Transcription Factors; C490034:Trim25 protein, mouse; D044767:Ubiquitin-Protein Ligases; C506440:Casp12 protein, mouse; D053454:Caspase 12; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9016-20
19447924
Cell Host Microbe. 2008 Mar 13;3(3):146-57
18329614
J Virol. 2002 Oct;76(19):9588-99
12208938
J Neuropsychol. 2008 Sep;2(2):477-99
19824176
J Biol Chem. 2001 Sep 7;276(36):33869-74
11448953
J Biol Chem. 2002 Jun 14;277(24):21836-42
11919205
J Immunol. 2008 Nov 15;181(10):7324-31
18981155
J Virol. 2008 Jan;82(1):335-45
17942531
Nature. 2007 Apr 19;446(7138):916-920
17392790
Blood. 2008 Dec 1;112(12):4574-84
18802009
Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5
17709747
J Biol Chem. 2005 Aug 19;280(33):29578-87
15975932
Nat Med. 2004 Dec;10(12):1366-73
15558055
Cell Death Differ. 2007 Jan;14(1):23-31
16977333
Nature. 2002 Mar 14;416(6877):194-9
11894098
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4133-8
18332441
J Immunol. 2006 Apr 15;176(8):4520-4
16585540
J Immunol. 2000 Oct 1;165(7):3959-65
11034404
Immunity. 2009 Feb 20;30(2):242-53
19200759
Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):582-7
17190814
J Biol Chem. 2007 May 25;282(21):15315-8
17395582
Virology. 2005 Mar 1;333(1):180-9
15708603
Nature. 2006 Apr 20;440(7087):1064-8
16625199
Immunity. 2009 Apr 17;30(4):556-65
19362020
Acta Biochim Pol. 2005;52(2):381-95
15933766
Cell Death Differ. 2007 Jan;14(1):44-55
17053807
J Immunol. 2005 Sep 1;175(5):2851-8
16116171
Nat Immunol. 2009 Mar;10(3):241-7
19221555
J Cell Biochem. 2001;80(3):441-54
11135374
Nat Immunol. 2010 Jan;11(1):63-9
19915568
Nat Immunol. 2003 May;4(5):432-3
12719735
Nature. 2004 May 6;429(6987):75-9
15129283
Cell Death Differ. 2007 Jan;14(1):10-22
16977329
Immunity. 2009 Apr 17;30(4):566-75
19362023
J Virol. 2007 Mar;81(6):2817-30
17215292
J Exp Med. 2009 Jan 16;206(1):79-87
19139171
Nat Immunol. 2004 Jul;5(7):730-7
15208624
J Virol. 2003 Dec;77(24):13203-13
14645577
Proc Natl Acad Sci U S A. 2007 May 1;104(18):7500-5
17460044
J Biol Chem. 2001 Apr 27;276(17):13935-40
11278723
Nature. 2000 Jan 6;403(6765):98-103
10638761
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1512-7
20080593
J Virol. 2007 Mar;81(6):2614-23
17192305
J Virol. 2008 Nov;82(21):10349-58
18715906
Nature. 2006 May 4;441(7089):101-5
16625202
J Biol Chem. 2006 Feb 3;281(5):2693-700
16317003
J Neurosci. 2004 Feb 25;24(8):1987-95
14985441
J Biol Chem. 2006 Jun 9;281(23):16016-24
16597616
J Virol. 2008 Jan;82(2):609-16
17977974
J Neurosci. 1997 Oct 1;17(19):7385-95
9295384