IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity

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The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV. IPS-1^−/− mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1^−/− mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection. Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection.

Vyšlo v časopise: IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity. PLoS Pathog 6(2): e32767. doi:10.1371/journal.ppat.1000757
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000757

Souhrn

Zdroje

1. Cdc 2008 West Nile virus activity–United States, 2007. MMWR 57 720 723

2. SamuelMA

DiamondMS

2006 Pathogensis of West NIle virus infection: a balance between virulence, innate and adaptive immunity, and viral evasion. J Virol 80 9349 9360

3. HayesEB

SejvarJ

ZakiS

LanciottiR

BodeA

2005 Virology, pathology, and clinical manifestations of West Nile Virus disease. Emerg Infect Dis 11 1174 1296

4. DebiasiRL

ParsonsJA

GrabertBE

2005 West Nile virus meningoencephalitis in an immunocompetent adolescent. Pediatr Neurol 33 217 219

5. EmigM

AppleDJ

2004 Severe West Nile virus disease in healthy adults. Clin Infec Dis 38 289 292

6. FischerSA

2008 Emerging viruses in transplantation: there is more to infection after transplant than CMV and EBV. Transplantation 86 1327 1339

7. SutharMS

GaleMJr

OwenDM

2009 Evasion and disruption of innate immune signalling by hepatitis C and West Nile viruses. Cell Microbiol 11 880 888

8. DaffisS

SamuelMA

KellerBC

GaleMJr

DiamondMS

2007 Cell-specific IRF-3 responses protect against West Nile virus infection by interferon-dependent and -independent mechanisms. PLoS Pathog 3 e106 doi:10.1371/journal.ppat.0030106

9. DaffisS

SamuelMA

SutharMS

KellerBC

GaleMJr

2008 Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection. J Virol 82 8465 8475

10. FredericksenBL

SmithM

KatzeMG

ShiPY

GaleMJr

2004 The host response to West Nile Virus infection limits viral spread through the activation of the interferon regulatory factor 3 pathway. J Virol 78 7737 7747

11. KellerBC

FredericksenBL

SamuelMA

MockRE

MasonPW

2006 Resistance to alpha/beta interferon is a determinant of west nile virus replication fitness and virulence. J Virol 80 9424 9434

12. SamuelMA

DiamondMS

2005 Alpha/beta interferon protects against lethal West Nile virus infection by restricting cellular tropism and enhancing neuronal survival. J Virol 79 13350 13361

13. KangDC

GopalkrishnanRV

WuQ

JankowskyE

PyleAM

2002 mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. PNAS 99 637 642

14. SumpterR

LooYM

FoyE

liK

YoneyamaM

2005 Regulating intracellular anti-viral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. J Virol 79 2689 2699

15. YoneyamaM

KikuchiM

NatsukawaT

ShinobuN

ImaizumiT

2004 The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5 730 737

16. YoneyamaM

KikuchiM

MatsumotoK

ImaizumiT

MiyagishiM

2005 Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 175 2851 2858

17. KatoH

TakeuchiO

Mikamo-SatohE

HiraiR

KawaiT

2008 Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 205 1601 1610

18. SaitoT

HiraiR

LooYM

OwenD

JohnsonCL

2007 Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. PNAS 104 582 587

19. LooYM

FornekJ

CrochetN

BajwaG

PerwitasariO

2008 Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 82 335 345

20. FredericksenBL

GaleMJr

2006 West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling. J Virol 80 2913 2923

21. FredericksenBL

KellerBC

FornekJ

KatzeMG

GaleMJr

2008 Establishment and maintenance of the innate antiviral response to West Nile virus involves both RIG-I and MDA5 signaling through IPS-1. J Virol 82 609 616

22. KatoH

TakeuchiO

SatoS

YoneyamaM

YamamotoM

2006 Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441 101 105

23. DaffisS

SamuelMA

SutharMS

GaleMJr

DiamondMS

2008 Toll-like receptor 3 has a protective role against West Nile virus infection. J Virol 82 10349 10358

24. WangT

TownT

AlexopoulouL

AndersonJF

FikrigE

2004 Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 10 1366 1373

25. TownT

BaiF

WangT

KaplanAT

QianF

2009 Toll-like receptor 7 mitigates lethal West Nile encephalitis via interleukin 23-dependent immune cell infiltration and homing. Immunity 30 242 253

26. LundJM

HsingL

PhamTT

RudenskyAY

2008 Coordination of early protective immunity to viral infection by regulatory T cells. Science 320 1220 1224

27. BelkaidY

RouseBT

2005 Natural regulatory T cells in infectious disease. Nat Immunol 6 353 360

28. LeonB

ArdavinC

2008 Monocyte-derived dendritic cells in innate and adaptive immunity. Immunol Cell Biol 86 320 324

29. JohnsonCL

GaleMJr

2006 CARD games between virus and host get a new player. Trends Immunol 27 1 4

30. FensterlV

WhiteCL

YamashitaM

SenGC

2008 Novel characteristics of the function and induction of murine p56 family proteins. J Virol 82 11045 11053

31. GrandvauxN

ServantMJ

tenOeverB

SenGC

BalachandranS

2002 Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. J Virol 76 5532 5539

32. ShresthaB

GottliebD

DiamondMS

2003 Infection and injury of neurons by West Nile encephalitis virus. J Virol 77 13203 13213

33. XiaoSY

GuzmanH

ZhangH

Travassos da RosaAP

TeshRB

2001 West Nile virus infection in the golden hamster (Mesocricetus auratus): a model for West Nile encephalitis. Emerg Infect Dis 7 714 721

34. ShresthaB

DiamondMS

2004 Role of CD8+ T cells in control of West Nile virus infection. J Virol 78 8312 8321

35. BrienJD

UhrlaubJL

Nikolich-ZugichJ

2007 Protective capacity and epitope specificity of CD8(+) T cells responding to lethal West Nile virus infection. Eur J Immunol 37 1855 1863

36. PurthaWE

MyersN

MitaksovV

SitatiE

ConnollyJ

2007 Antigen-specific cytotoxic T lymphocytes protect against lethal West Nile virus encephalitis. Eur J Immunol 37 1845 1854

37. SchaferA

WhitmoreAC

KonopkaJL

JohnstonRE

2009 Replicon particles of venezuelan equine encephalitis virus as a reductionist murine model for encephalitis. J Virol 83 4275 4286

38. KatoH

SatoS

YoneyamaM

YamamotoM

UematsuS

2005 Cell type-specific involvement of RIG-I in antiviral response. Immunity 23 19 28

39. DiamondMS

SitatiEM

FriendLD

HiggsS

ShresthaB

2003 A critical role for induced IgM in the protection against West Nile virus infection. J Exp Med 198 1853 1862

40. DiamondMS

ShresthaB

MarriA

MahanD

EngleM

2003 B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus. J Virol 77 2578 2586

41. HildnerK

EdelsonBT

PurthaWE

DiamondM

MatsushitaH

2008 Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322 1097 1100

42. Lopez-BravoM

ArdavinC

2008 In vivo induction of immune responses to pathogens by conventional dendritic cells. Immunity 29 343 351

43. AnghelinaD

ZhaoJ

TrandemK

PerlmanS

2009 Role of regulatory T cells in coronavirus-induced acute encephalitis. Virology 385 358 367

44. RuckwardtTJ

BonaparteKL

NasonMC

GrahamBS

2009 Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities. J Virol 83 3019 3028

45. LanteriMC

O'BrienKM

PurthaWE

CameronMJ

LundJM

2009 Tregs control the development of symptomatic West Nile virus infection in humans and mice. J Clin Invest 119 3266 3277

46. Asselin-PaturelC

TrinchieriG

2005 Production of type I interferons: plasmacytoid dendritic cells and beyond. J Exp Med 202 461 465

47. SilvaMC

Guerrero-PlataA

GilfoyFD

GarofaloRP

MasonPW

2007 Differential activation of human monocyte-derived and plasmacytoid dendritic cells by West Nile virus generated in different host cells. J Virol 81 13640 13648

48. PurthaWE

ChachuKA

VirginHW

DiamondMS

2008 Early B-cell activation after West Nile virus infection requires alpha/beta interferon but not antigen receptor signaling. J Virol 82 10964 10974

49. CoroES

ChangWL

BaumgarthN

2006 Type I IFN receptor signals directly stimulate local B cells early following influenza virus infection. J Immunol 176 4343 4351

50. FinkK

LangKS

Manjarrez-OrdunoN

JuntT

SennBM

2006 Early type I interferon-mediated signals on B cells specifically enhance antiviral humoral responses. Eur J Immunol 36 2094 2105

51. KolumamGA

ThomasS

ThompsonLJ

SprentJ

Murali-KrishnaK

2005 Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J Exp Med 202 637 650

52. ThompsonLJ

KolumamGA

ThomasS

Murali-KrishnaK

2006 Innate Inflammatory Signals Induced by Various Pathogens Differentially Dictate the IFN-I Dependence of CD8 T Cells for Clonal Expansion and Memory Formation. J Immunol 177 1746 1754

53. Havenar-DaughtonC

KolumamGA

Murali-KrishnaK

2006 Cutting Edge: The direct action of type I IFN on CD4 T cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection. J Immunol 176 3315 3319

54. GerosaF

GobbiA

ZorziP

BurgS

BriereF

2005 The reciprocal interaction of NK cells with plasmacytoid or myeloid dendritic cells profoundly affects innate resistance functions. J Immunol 174 727 734

55. ShresthaB

SamuelMA

DiamondMS

2006 CD8+ T cells require perforin to clear West Nile virus from infected neurons. J Virol 80 119 129

56. WangY

LobigsM

LeeE

MullbacherA

2003 CD8+ T cells mediate recovery and immunopathology in West Nile virus encephalitis. J Virol 77 13323 13334

57. BrienJD

UhrlaubJL

Nikolich-ZugichJ

2008 West Nile virus-specific CD4 T cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protection. J Immunol 181 8568 8575

58. SitatiEM

DiamondMS

2006 CD4+ T-cell responses are required for clearance of West Nile virus from the central nervous system. J Virol 80 12060 12069

59. WakimLM

WaithmanJ

Van RooijenN

HeathWR

CarboneFR

2008 Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science 319 198 202

60. La CavaA

2008 Tregs are regulated by cytokines: implications for autoimmunity. Autoimmun Rev 8 83 87

61. KumarH

KawaiT

KatoH

SatoS

TakahashiK

2006 Essential role of IPS-1 in innate immune responses against RNA viruses. J Exp Med 203 1795 1803

62. SamuelMA

WhitbyK

KellerBC

MarriA

BarchetW

2006 PKR and RNase L contribute to protection against lethal West Nile Virus infection by controlling early viral spread in the periphery and replication in neurons. J Virol 80 7009 7019

63. LinkeS

EllerbrokH

NiedrigM

NitscheA

PauliG

2007 Detection of West Nile virus lineages 1 and 2 by real-time PCR. J Virol Met 146 355 358

64. SaitoT

OwenDM

JiangF

MarcotrigianoJ

GaleMJr

2008 Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature 454 523 527

65. ShabmanRS

MorrisonTE

MooreC

WhiteL

SutharMS

2007 Differential induction of type I interferon responses in myeloid dendritic cells by mosquito and mammalian-cell-derived alphaviruses. J Virol 81 237 247