Skip to main content

Advertisement

SpringerLink
Log in

Reading the viral signature by Toll-like receptors and other pattern recognition receptors

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Successful host defense against viral infections relies on early production of type I interferon (IFN) and subsequent activation of a cellular cytotoxic response. The acute IFN and inflammatory response against virus infections is mediated by cellular pattern-recognition receptors (PRRs) that recognize specific molecular structures on viral particles or products of viral replication. Toll-like receptors (TLRs) constitute a class of membrane-bound PRRs capable of detecting microbial infections. While TLR2 and TLR4, which were first identified to recognize Gram-positive and Gram-negative bacteria, respectively, sense specific viral proteins on the cell surface, TLRs 3, 7, 8, and 9 serve as receptors for viral nucleic acids in endosomic compartments. In addition to TLRs, cells express cytoplasmic PRRs such as the RNA helicase retinoic acid inducible gene I and the kinase double-stranded RNA-activated protein kinase R, both of which sense dsRNA, a characteristic signature of viral replication, and initiate a protective cellular response. Here we review the recent progress in our understanding of PRRs and viral infections and discuss the molecular and cellular responses evoked by virus-activated PRRs. Finally, we look into what is currently known about the role of PRRs in viral infections in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CARD :

Caspase-associated recruitment domain

CMV :

Cytomegalovirus

CpG :

Cytosine-phosphate-guanine

DC :

Dendritic cell

dsRNA :

Double-stranded RNA

eIF :

Eukaryotic initiation factor

HIV :

Human immunodeficiency virus

HSP :

Heat-shock protein

HSV :

Herpes simplex virus

IFN :

Interferon

IKK :

Inhibitory protein κB kinase

IL :

Interleukin

IRAK :

Interleukin 1 receptor associated kinase

IRF :

Interferon regulatory factor

LRR :

Leucine-rich region

Mal :

MyD88-adapter-like

MAP :

Mitogen-activated protein

MKK :

MAP kinase kinase

MyD :

Myeloid differentiation factor

NF :

Nuclear factor

NK :

Natural killer

NOD :

Nucleotide-binding oligomerization domain

PAMP :

Pathogen-associated molecular pattern

pDC :

Plasmacytoid dendritic cell

PKR :

dsRNA-activated protein kinase R

PolyIC :

Poly-rI:rC

PRR :

Pattern-recognition receptor

RIG :

Retinoic acid inducible gene

Rip :

Receptor interacting protein

RSV :

Respiratory syncytial virus

ssRNA :

Single-stranded RNA

TAK :

Transforming growth factor β activated kinase

TBK :

TRAF family member associated NF-κ activator binding kinase

TIR :

Toll/IL-1 receptor

TLR :

Toll-like receptor

TNF :

Tumor necrosis factor

TRAF :

TNF receptor-associated factor

TRAM :

TRIF-related adaptor molecule

TRIF :

TIR domain containing adaptor inducing interferon β

VSV :

Vesicular stomatitis virus

VV :

Vaccinia virus

References

  1. Beutler B (2004) Inferences, questions and possibilities in Toll-like receptor signalling. Nature 430:257–263

    CAS  PubMed  Google Scholar 

  2. Kopp EB, Medzhitov R (1999) The Toll-receptor family and control of innate immunity. Curr Opin Immunol 11:13–18

    Google Scholar 

  3. Beg AA (2002) Endogenous ligands of Toll-like receptors: implications for regulating inflammatory and immune responses. Trends Immunol 23:509–512

    CAS  PubMed  Google Scholar 

  4. Kaisho T, Akira S (2003) Regulation of dendritic cell function through Toll-like receptors. Curr Mol Med 3:373–385

    CAS  PubMed  Google Scholar 

  5. O’Neill LA, Fitzgerald KA, Bowie AG (2003) The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol 24:286–290

    Article  PubMed  Google Scholar 

  6. Wagner H (2004) The immunobiology of the TLR9 subfamily. Trends Immunol 25:381–386

    CAS  PubMed  Google Scholar 

  7. Matsumoto M, Funami K, Tanabe M, Oshiumi H, Shingai M, Seto Y, Yamamoto A, Seya T (2003) Subcellular localization of toll-like receptor 3 in human dendritic cells. J Immunol 171:3154–3162

    Google Scholar 

  8. Medzhitov R, Preston-Hutlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397

    Article  CAS  PubMed  Google Scholar 

  9. Hoffmann JA (2003) The immune response of Drosophila. Nature 426:33–38

    CAS  PubMed  Google Scholar 

  10. Latz E, Schoenemeyer A, Visintin A, Fitzgerald KA, Monks BG, Knetter CF, Lien E, Nilsen NJ, Espevik T, Golenbock DT (2004) TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol 5:190–198

    Google Scholar 

  11. Mizel SB, West AP, Hantgan RR (2003) Identification of a sequence in human toll-like receptor 5 required for the binding of Gram-negative flagellin. J Biol Chem 278:23624–23629

    CAS  PubMed  Google Scholar 

  12. Miyake K (2004) Innate recognition of lipopolysaccharide by Toll-like receptor 4-MD-2. Trends Microbiol 12:186–192

    Google Scholar 

  13. Inohara N, Nunez G (2003) NODs: intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol 3:371–382

    Google Scholar 

  14. Athman R, Philpott D (2004) Innate immunity via Toll-like receptors and Nod proteins. Curr Opin Microbiol 7:25–32

    CAS  PubMed  Google Scholar 

  15. Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jehanno M, Viala J, Tedin K, Taha MK, Labigne A, Zahringer U, Coyle AJ, DiStefano PS, Bertin J, Sansonetti PJ, Philpott DJ (2003) Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 300:1584–1587

    CAS  PubMed  Google Scholar 

  16. Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nunez G (2003) Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem 278:5509–5512

    CAS  PubMed  Google Scholar 

  17. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5:730–737

    Google Scholar 

  18. Williams BR (2001) Signal integration via PKR. Sci STKE RE2

  19. Zamanian-Daryoush M, Mogensen TH, Didonato JA, Williams BR (2000) NF-κB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-κB-inducing kinase and IκB kinase. Mol Cell Biol 20:1278–1290

    CAS  PubMed  Google Scholar 

  20. Chu WM, Ostertag D, Li ZW, Chang L, Hu Y, Williams B, Perrault J, Karin M (1999) JNK2 and IKKβ are required for activating the innate response to viral infection. Immunity 11:721–731

    CAS  PubMed  Google Scholar 

  21. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511

    Google Scholar 

  22. Dunne A, O’Neill LA (2003) The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE RE3

  23. Jiang Z, Zamanian-Daryoush M, Nie H, Silva AM, Williams BR, Li X (2003) Poly (I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFκB and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR. J Biol Chem 278:16713–16719

    CAS  PubMed  Google Scholar 

  24. Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K, Akira S (2003) Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-κB and IFN-regulatory factor-3, in the Toll-like receptor signaling. J Immunol 171:4304–4310

    Google Scholar 

  25. Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM, Maniatis T (2003) IKKε and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4:491–496

    Google Scholar 

  26. Sharma S, tenOever BR, Grandvaux N, Zhou GP, Lin R, Hiscott J (2003) Triggering the interferon antiviral response through an IKK-related pathway. Science 300:1148–1151

    CAS  PubMed  Google Scholar 

  27. Sato M, Suemori H, Hata N, Asagiri M, Ogasawara K, Nakao K, Nakaya T, Katsuki M, Noguchi S, Tanaka N, Taniguchi T (2000) Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-α/β gene induction. Immunity 13:539–548

    Google Scholar 

  28. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301:640–643

    CAS  PubMed  Google Scholar 

  29. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196–200

    Google Scholar 

  30. Inohara N, Koseki T, Lin J, del Peso L, Lucas PC, Chen FF, Ogura Y, Nunez G (2000) An induced proximity model for NF-κB activation in the Nod1/RICK and RIP signaling pathways. J Biol Chem 275:27823–27831

    CAS  PubMed  Google Scholar 

  31. McCarthy JV, Ni J, Dixit VM (1998) RIP2 is a novel NF-κB-activating and cell death-inducing kinase. J Biol Chem 273:16968–16975

    CAS  PubMed  Google Scholar 

  32. Perry AK, Chow EK, Goodnough JB, Yeh WC, Cheng G (2004) Differential requirement for TANK-binding kinase-1 in type I interferon responses to Toll-like receptor activation and viral infection. J Exp Med 199:1651–1658

    CAS  PubMed  Google Scholar 

  33. Hemmi H, Takeuchi O, Sato S, Yamamoto M, Kaisho T, Sanjo H, Kawai T, Hoshino K, Takeda K, Akira S (2004) The roles of two IκB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J Exp Med 199:1641–1650

    CAS  PubMed  Google Scholar 

  34. Gil J, Alcami J, Esteban M (2000) Activation of NF-κB by the dsRNA-dependent protein kinase, PKR involves the IκB kinase complex. Oncogene 19:1369–1378

    CAS  PubMed  Google Scholar 

  35. Mogensen TH, Paludan SR (2001) Molecular pathways in virus-induced cytokine production. Microbiol Mol Biol Rev 65:131–150

    CAS  PubMed  Google Scholar 

  36. Smith EJ, Marie I, Prakash A, Garcia-Sastre A, Levy DE (2001) IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or IκB kinase but is blocked by vaccinia virus E3L protein. J Biol Chem 276:8951–8957

    CAS  PubMed  Google Scholar 

  37. Gil J, Garcia MA, Gomez-Puertas P, Guerra S, Rullas J, Nakano H, Alcami J, Esteban M (2004) TRAF family proteins link PKR with NF-κB activation. Mol Cell Biol 24:4502–4512

    CAS  PubMed  Google Scholar 

  38. Silva AM, Whitmore M, Xu Z, Jiang Z, Li X, Williams BR (2004) Protein kinase R (PKR) interacts with and activates mitogen activated protein kinase kinase 6 (MKK6) in response to double stranded RNA stimulation. J Biol Chem 279:37670–37676

    CAS  PubMed  Google Scholar 

  39. Horng T, Barton GM, Medzhitov R (2001) TIRAP: an adapter molecule in the Toll signaling pathway. Nat Immunol 2:835–841

    Google Scholar 

  40. Hsu LC, Park JM, Zhang K, Luo JL, Maeda S, Kaufman RJ, Eckmann L, Guiney DG, Karin M (2004) The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428:341–345

    CAS  PubMed  Google Scholar 

  41. Malmgaard L (2004) Induction and regulation of IFNs during viral infections. J Interferon Cytokine Res 24:439–454

    CAS  PubMed  Google Scholar 

  42. Boehme KW, Compton T (2004) Innate sensing of viruses by toll-like receptors. J Virol 78:7867–7873

    CAS  PubMed  Google Scholar 

  43. Compton T, Kurt-Jones EA, Boehme KW, Belko J, Latz E, Golenbock DT, Finberg RW (2003) Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol 77:4588–4596

    CAS  PubMed  Google Scholar 

  44. Compton T (2004) Receptors and immune sensors: the complex entry path of human cytomegalovirus. Trends Cell Biol 14:5–8

    CAS  PubMed  Google Scholar 

  45. Bieback K, Lien E, Klagge IM, Avota E, Schneider-Schaulies J, Duprex WP, Wagner H, Kirschning CJ, Ter M, V, Schneider-Schaulies S (2002) Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signaling. J Virol 76:8729–8736

    Article  CAS  PubMed  Google Scholar 

  46. Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, Walsh EE, Freeman MW, Golenbock DT, Anderson LJ, Finberg RW (2000) Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol 1:398–401

    Google Scholar 

  47. Triantafilou K, Triantafilou M (2004) Coxsackievirus B4-induced cytokine production in pancreatic cells is mediated through toll-like receptor 4. J Virol 78:11313–11320

    CAS  PubMed  Google Scholar 

  48. Rassa JC, Meyers JL, Zhang Y, Kudaravalli R, Ross SR (2002) Murine retroviruses activate B cells via interaction with toll-like receptor 4. Proc Natl Acad Sci U S A 99:2281–2286

    CAS  PubMed  Google Scholar 

  49. Burzyn D, Rassa JC, Kim D, Nepomnaschy I, Ross SR, Piazzon I (2004) Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus. J Virol 78:576–584

    CAS  PubMed  Google Scholar 

  50. Whitley RJ (2001) Herpes simplex virus. In: Knipe DM, Howley PM (eds) Fields virology, vol 2. Lippincott, Williams & Wilkins, Philadelphia, pp 2461–2509

  51. Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J Biol Chem 277:15028–15034

    Article  CAS  PubMed  Google Scholar 

  52. Taddeo B, Esclatine A, Roizman B (2002) The patterns of accumulation of cellular RNAs in cells infected with a wild-type and a mutant herpes simplex virus 1 lacking the virion host shutoff gene. Proc Natl Acad Sci U S A 99:17031–17036

    CAS  PubMed  Google Scholar 

  53. Kurt-Jones EA, Chan M, Zhou S, Wang J, Reed G, Bronson R, Arnold MM, Knipe DM, Finberg RW (2004) Herpes simplex virus 1 interaction with Toll-like receptor 2 contributes to lethal encephalitis. Proc Natl Acad Sci U S A 101:1315–1320

    CAS  PubMed  Google Scholar 

  54. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413:732–738

    Article  CAS  PubMed  Google Scholar 

  55. Matsumoto M, Funami K, Oshiumi H, Seya T (2004) Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. Microbiol Immunol 48:147–154

    CAS  PubMed  Google Scholar 

  56. Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, Alexopoulou L, Flavell RA, Beutler B (2004) Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A 101:3516–3521

    PubMed  Google Scholar 

  57. Lee J, Chuang TH, Redecke V, She L, Pitha PM, Carson DA, Raz E, Cottam HB (2003) Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Proc Natl Acad Sci U S A 100:6646–6651

    CAS  PubMed  Google Scholar 

  58. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303:1526–1529

    CAS  PubMed  Google Scholar 

  59. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529–1531

    CAS  PubMed  Google Scholar 

  60. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA (2004) Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc Natl Acad Sci U S A 101:5598–5603

    CAS  PubMed  Google Scholar 

  61. Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A (2003) Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med 198:513–520

    CAS  PubMed  Google Scholar 

  62. Krug A, Luker GD, Barchet W, Leib DA, Akira S, Colonna M (2004) Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 103:1433–1437

    CAS  PubMed  Google Scholar 

  63. Kariko K, Ni H, Capodici J, Lamphier M, Weissman D (2004) mRNA is an endogenous ligand for Toll-like receptor 3. J Biol Chem 279:12542–12550

    CAS  PubMed  Google Scholar 

  64. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408:740–745

    CAS  PubMed  Google Scholar 

  65. Diebold SS, Montoya M, Unger H, Alexopoulou L, Roy P, Haswell LE, Al Shamkhani A, Flavell R, Borrow P, Reis e Sousa C (2003) Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 424:324–328

    CAS  PubMed  Google Scholar 

  66. Eickhoff J, Hanke M, Stein-Gerlach M, Kiang TP, Herzberger K, Habenberger P, Muller S, Klebl B, Marschall M, Stamminger T, Cotten M (2004) RICK activates a NF-κB-dependent anti-human cytomegalovirus response. J Biol Chem 279:9642–9652

    CAS  PubMed  Google Scholar 

  67. Kobayashi K, Inohara N, Hernandez LD, Galan JE, Nunez G, Janeway CA, Medzhitov R, Flavell RA (2002) RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems. Nature 416:194–199

    CAS  PubMed  Google Scholar 

  68. Chin AI, Dempsey PW, Bruhn K, Miller JF, Xu Y, Cheng G (2002) Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Nature 416:190–194

    CAS  PubMed  Google Scholar 

  69. Maitra RK, McMillan NA, Desai S, McSwiggen J, Hovanessian AG, Sen G, Williams BR, Silverman RH (1994) HIV-1 TAR RNA has an intrinsic ability to activate interferon-inducible enzymes. Virology 204:823–827

    CAS  PubMed  Google Scholar 

  70. Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–995

    Google Scholar 

  71. Baldridge JR, McGowan P, Evans JT, Cluff C, Mossman S, Johnson D, Persing D (2004) Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents. Expert Opin Biol Ther 4:1129–1138

    CAS  PubMed  Google Scholar 

  72. Hoebe K, Janssen EM, Kim SO, Alexopoulou L, Flavell RA, Han J, Beutler B (2003) Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways. Nat Immunol 4:1223–1229

    Google Scholar 

  73. Ahonen CL, Doxsee CL, McGurran SM, Riter TR, Wade WF, Barth RJ, Vasilakos JP, Noelle RJ, Kedl RM (2004) Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN. J Exp Med 199:775–784

    CAS  PubMed  Google Scholar 

  74. Honda K, Sakaguchi S, Nakajima C, Watanabe A, Yanai H, Matsumoto M, Ohteki T, Kaisho T, Takaoka A, Akira S, Seya T, Taniguchi T (2003) Selective contribution of IFN-α/β signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection. Proc Natl Acad Sci U S A 100:10872–10877

    CAS  PubMed  Google Scholar 

  75. Asselin-Paturel C, Boonstra A, Dalod M, Durand I, Yessaad N, Dezutter-Dambuyant C, Vicari A, O’Garra A, Biron C, Briere F, Trinchieri G (2001) Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat Immunol 2:1144–1150

    Google Scholar 

  76. Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, Ho S, Antonenko S, Liu YJ (1999) The nature of the principal type 1 interferon-producing cells in human blood. Science 284:1835–1837

    CAS  PubMed  Google Scholar 

  77. Kadowaki N, Antonenko S, Lau JY, Liu YJ (2000) Natural interferon α/β-producing cells link innate and adaptive immunity. J Exp Med 192:219–226

    Article  CAS  PubMed  Google Scholar 

  78. Haeberle HA, Takizawa R, Casola A, Brasier AR, Dieterich HJ, van Rooijen N, Gatalica Z, Garofalo RP (2002) Respiratory syncytial virus-induced activation of nuclear factor-κB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways. J Infect Dis 186:1199–1206

    CAS  PubMed  Google Scholar 

  79. Psarras S, Papadopoulos NG, Johnston SL (2004) Pathogenesis of respiratory syncytial virus bronchiolitis-related wheezing. Paediatr Respir Rev 5 [Suppl A]:S179–S184

  80. Hochrein H, Schlatter B, O’Keeffe M, Wagner C, Schmitz F, Schiemann M, Bauer S, Suter M, Wagner H (2004) Herpes simplex virus type-1 induces IFN-{d} production via Toll-like receptor 9-dependent and -independent pathways. Proc Natl Acad Sci U S A 101:11416–11421

    CAS  PubMed  Google Scholar 

  81. Miettinen M, Sareneva T, Julkunen I, Matikainen S (2001) IFNs activate toll-like receptor gene expression in viral infections. Genes Immun 2:349–355

    CAS  PubMed  Google Scholar 

  82. Haynes LM, Moore DD, Kurt-Jones EA, Finberg RW, Anderson LJ, Tripp RA (2001) Involvement of toll-like receptor 4 in innate immunity to respiratory syncytial virus. J Virol 75:10730–10737

    CAS  PubMed  Google Scholar 

  83. Ehl S, Bischoff R, Ostler T, Vallbracht S, Schulte-Monting J, Poltorak A, Freudenberg M (2004) The role of Toll-like receptor 4 versus interleukin-12 in immunity to respiratory syncytial virus. Eur J Immunol 34:1146–1153

    Google Scholar 

  84. Tal G, Mandelberg A, Dalal I, Cesar K, Somekh E, Tal A, Oron A, Itskovich S, Ballin A, Houri S, Beigelman A, Lider O, Rechavi G, Amariglio N (2004) Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease. J Infect Dis 189:2057–2063

    CAS  PubMed  Google Scholar 

  85. Dupuis S, Jouanguy E, Al Hajjar S, Fieschi C, Al Mohsen IZ, Al Jumaah S, Yang K, Chapgier A, Eidenschenk C, Eid P, Al Ghonaium A, Tufenkeji H, Frayha H, Al Gazlan S, Al Rayes H, Schreiber RD, Gresser I, Casanova JL Impaired response to interferon-α/β and lethal viral disease in human STAT1 deficiency. Nat Genet 33:388–391

  86. Biron CA, Byron KS, Sullivan JL (1989) Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med 320:1731–1735

    CAS  PubMed  Google Scholar 

  87. Lint A van, Ayers M, Brooks AG, Coles RM, Heath WR, Carbone FR (2004) Herpes simplex virus-specific CD8+ T cells can clear established lytic infections from skin and nerves and can partially limit the early spread of virus after cutaneous inoculation. J Immunol 172:392–397

    Google Scholar 

  88. Bowie A, Kiss-Toth E, Symons JA, Smith GL, Dower SK, O’Neill LA (2000) A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling. Proc Natl Acad Sci U S A 97:10162–10167

    CAS  PubMed  Google Scholar 

  89. Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264

    Article  CAS  PubMed  Google Scholar 

  90. Edelmann KH, Richardson-Burns S, Alexopoulou L, Tyler KL, Flavell RA, Oldstone MB (2004) Does Toll-like receptor 3 play a biological role in virus infections? Virology 322:231–238

    CAS  PubMed  Google Scholar 

  91. Hoebe K, Du X, Georgel P, Janssen E, Taβ K, Kim SO, Goode J, Lin P, Mann N, Mudd S, Crozat K, Sovath S, Han J, Beutler B (2003) Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424:743–748

    CAS  PubMed  Google Scholar 

  92. Spriggs MK (1996) One step ahead of the game: viral immunomodulatory molecules. Annu Rev Immunol 14:101–130

    CAS  PubMed  Google Scholar 

  93. Reference deleted

  94. Harte MT, Haga IR, Maloney G, Gray P, Reading PC, Bartlett NW, Smith GL, Bowie A, O’Neill LA (2003) The poxvirus protein A52R targets Toll-like receptor signaling complexes to suppress host defense. J Exp Med 197:343–351

    CAS  PubMed  Google Scholar 

  95. Kumar A, Yang YL, Flati V, Der S, Kadereit S, Deb A, Haque J, Reis L, Weissmann C, Williams BR (1997) Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-κB. EMBO J 16:406–416

    CAS  PubMed  Google Scholar 

  96. Yang YL, Reis LF, Pavlovic J, Aguzzi A, Schafer R, Kumar A, Williams BR, Aguet M, Weissmann C (1995) Deficient signaling in mice devoid of double-stranded RNA- dependent protein kinase. EMBO J 14:6095–6106

    CAS  PubMed  Google Scholar 

  97. Stewart MJ, Blum MA, Sherry B (2003) PKR’s protective role in viral myocarditis. Virology 314:92–100

    CAS  PubMed  Google Scholar 

  98. Balachandran S, Roberts PC, Brown LE, Truong H, Pattnaik AK, Archer DR, Barber GN (2000) Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection. Immunity 13:129–141

    Google Scholar 

  99. Kim TK, Maniatis T (1998) The mechanism of transcriptional synergy of an in vitro assembled interferon-β enhanceosome. Mol Cell 1:119–129

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank Drs. Andrew G. Bowie and Douglas T. Golenbock for sharing unpublished results. This work was supported by grants from the Danish Health Science Research Council (grant nos. 22-02-0144 and 22-03-0183) and the Lundbeck Foundation.

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Skejby Hospital, Aarhus, Denmark

    Trine H. Mogensen

  2. Department of Medical Microbiology and Immunology, University of Aarhus, Bartholin Building, 8000, Aarhus C, Denmark

    Søren R. Paludan

Authors
  1. Trine H. Mogensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Søren R. Paludan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Søren R. Paludan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mogensen, T.H., Paludan, S.R. Reading the viral signature by Toll-like receptors and other pattern recognition receptors. J Mol Med 83, 180–192 (2005). https://doi.org/10.1007/s00109-004-0620-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-004-0620-6

Keywords

Search

Navigation