Activation of innate immune system during viral infection: Role of pattern-recognition receptors (PRRs) in viral infection

Journal of Bacteriology and Virology

Volumn 39, Issue 3, 2009, Pages 145-157

  Jun, Eun Jung ^a   Kim, Yoo Kyum ^a  

^a University of Ulsan College of Medicine   (South Korea)

Author keywords

Innate immunity; PAMP; RIG I like receptor; Toll like receptor; Viral infection

Indexed keywords

DNA; INTERFERON REGULATORY FACTOR; PATTERN RECOGNITION RECEPTOR; RETINOIC ACID INDUCIBLE PROTEIN I; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; TOLL LIKE RECEPTOR 9;

ADAPTIVE IMMUNITY; ADENOVIRUS; ARTICLE; HEPATITIS A VIRUS; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE RESPONSE; IMMUNOREACTIVITY; INFLUENZA VIRUS; INNATE IMMUNITY; MACROPHAGE; NONHUMAN; PARAMYXOVIRUS; PROTEIN FUNCTION; REGULATORY MECHANISM; SIMIAN VIRUS; T LYMPHOCYTE; UPREGULATION; VACCINIA VIRUS; VIRUS IMMUNITY; VIRUS INFECTION;

EID: 77953510207     PISSN: 15982467     EISSN: None     Source Type: Journal    
DOI: 10.4167/jbv.2009.39.3.145     Document Type: Article

References (101)

1. Janeway CA, Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol 1989;54 Pt 1:1-13.
2. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol 2004;4:499-511.
3. Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001;2:675-80.
4. Brown GD. Dectin-l: a signaling non-TLR pattern-recognition receptor. Nat Rev Immunol 2006;6:33-43.
5. Meylan E, Tschopp J, Karin M. Intracellular pattern recognition receptors in the host response. Nature 2006;442:39-44.
6. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol 2003;21:335-76.
7. Takeuchi O, Akira S. Innate immunity to virus infection. Immunol Rev 2009;227:75-86.
8. Lee MS, Kim YI Signaling pathways downstream of patternrecognition receptors and their cross talk. Annu Rev Biochem 2007;76:447-80.
9. Lee MS, Kim YI Pattern-recognition receptor signaling initiated from extracellular,membrane, and cytoplasmic space. Mol Cells 2007;23:1-10.
10. Kawai T, Akira S. Innate immune recognition of viral infection. Nat Immunol 2006;7:131-7
11. Aliprantis AO, Yang RE, Mark MR, Suggett S, Devaux B, Radolf JD, Klimpel GR, Godowski P, Zychlinsky A. Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science 1999;285:736-9.
12. Brightbill HD, Libraty DH, Krutzik SR, Yang RE, Belisle JT, Bleharski JR, Maitland M, Norgard MY, Plevy SE, Smale ST, Brennan PJ, Bloom BR, Godowski PJ, Modlin RL. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 1999;285:732-6.
13. Hirschfeld M, Kirschning CJ, Schwandner R, Wesche H, Weis JH, Wooten RM, Weis JJ. Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2. J Immunol 1999;163:2382-6.
14. Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 1999;162:3749-52.
15. Lien E, Sellati TJ, Yoshimura A, Flo TH, Rawadi G, Finberg RW, Carroll JD, Espevik T, Ingalls RR, Radolf JD, olenbock DT. Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products. J Bioi Chern 1999; 274:33419-25.
16. Poltorak A, He X, Smimova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/lOScCr mice: mutations in Tlr4 gene. Science 1998;282:2085-8.
17. Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CI Peptidog1ycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chern 1999;274:17406-9.
18. Takeuchi O, Kaufmann A, Grote K, Kawai T, Hoshino K, Morr M, Muhlradt PF, Akira S. Cutting edge: preferentially the R-stereoisomer of the mycoplasmal lipopeptidemacrophage-activating lipopeptide-2 activatesimmune cells through a toll-like receptor 2- andMyD88-dependent signaling pathway. J Immunol 2000;164:554-7.
19. Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D. Cutting edge: recognition of Gram-positive bacterialcell wall componentsby the innateimmunesystem occursvia Toll-like receptor2. J Immunol 1999;163:1-5.
20. Uematsu S, Akira S. Toll-like receptors and Type I interferons. J Biol Chern 2007;282:15319-23
21. Katze MG, He Y, GaleM Jr. Virusesand interferon: a fight for supremacy. Nat Rev Immunol 2002;2:675-87.
22. Sadler AI, Williams BR. Interferon-inducible antiviral effectors. Nat Rev Immunol 2008;8:559-68.
23. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007;449:819-26.
24. Hashimoto C, Hudson KL, Anderson KV. The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein. Cell 1988;52: 269-79.
25. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/ cactus controls the potent antifungal response in Drosophila adults. Cell 1996;86:973-83.
26. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Tollprotein signals activation of adaptive immunity. Nature 1997;388:394-7.
27. Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF. A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci USA 1998;95:588-93.
28. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783-801.
29. Mogensen TH, Paludan SR. Reading the viral signatureby Toll-like receptors and oilier pattern recognition receptors. J Mol Med 2005;83:180-92.
30. Barton GM. Viral recognition by Toll-like receptors. Semin Immunol 2007;19:33-40.
31. Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayarn P, Matsushima N, Lee H, Yoo OJ, Lee JO. Crystal structure of theTLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 2007;130:906-17.
32. Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO. Crystal structure of the TLRl-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 2007; 130:1071-82.
33. Matsumoto M, Funami K, Tanabe M, Oshiumi H, Shingai M, Seto Y, Yamamoto A, Seya T. Subcellular localization of Toll-like receptor 3 in humandendritic cells. J Immunol 2003; 171:3154-62.
34. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNAand activation of NF-kappaB by Toll-like receptor 3. Nature 2001;413:732-8.
35. Edelmann KH, Richardson-Bums S, Alexopoulou L, Tyler KL, Flavell RA, Oldstone ME. Docs Toll-like receptor 3 playa biologicalrole in virus infections? Virology 2004;322: 231-8.
36. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004; 303:1529-31.
37. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA. Recognition of singlestranded RNA viruses by Toll-like receptor7. Proc Nat1 Acad Sci USA 2004;101:5598-603.
38. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004;303:1526-9
39. Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, KIinman DM. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995; 374:546-9.
40. Bauer S, Kirschning CJ, Hacker H, Redecke V, Hausmarm S, Akira S, Wagner H, Lipford GB. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA 2001;98:9237-42.
41. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S. A Toll-like receptor recognizes bacterial DNA. Nature 2000; 408:740-5.
42. Krieg AM. CpG motifs in bacterial DNAand their immune effects. AnnuRev Immunol 2002;20:709-60.
43. Hacker H, Vabulas RM, Takeuchi O, Hoshino K, Akira S, Wagner H. Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumornecrosis factor receptor-associated factor (TRAF) 6. J Exp Med 2000; 192:595-600
44. Schnare M, Holt AC, Takeda K, Akira S, Medzhitov R. Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Curr BioI 2000; 10:1139-42.
45. Krug A, Luker GD, Barchet W, Leib DA, Akira S, Colonna M. Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 2004;103:1433-7.
46. Lnnd J, Sato A, Akira S, Medzhitov R, Iwasaki A. Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med 2003;198:513-20.
47. Delale T, Paquin A, Asselin-Paturel C, Dalod M, Brizard G, Bates EE, Kastner P, Chan S, Akira S, Vicari A, Biron CA, Trinchieri G, Briere F. MyD88-dependent and -independent murine cytomegalovirus sensing for IFN-alpha release and initiation of immnne responses in vivo. J Immunol 2005; 175:6723-32.
48. Krug A, French AR, Barchet W, Fischer JA, Dzionek A, Pingel IT, Orihuela MM, Akira S, Yokoyama WM, Colonna M. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity 2004;21:107-19.
49. Randall RE, Goodboum S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 2008;89:1-47.
50. Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K. Evidence for licensing of lFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptordependent gene induction program. Proc Natl Acad Sci USA 2006;103:15136-41.
51. Levy DE, Marie IJ. RiGging an antiviral defense--it's in the CARDs. Nat Immunol 2004;5:699-701.
52. Takaoka A, Taniguchi T. Cytosolic DNA recognition for triggering innate immune responses. Adv Drug Deliv Rev 2008;60:847-57.
53. Hemmi H, Takeuchi O, Sato S, Yamamoto M, Kaisho T, Sanjo H, Kawai T, Hoshino K, Takeda K, Akira S. The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J Exp Med 2004;199:1641-50.
54. Lopez CB, Moltedo B, Alexopoulou L, Bonifaz L, Flavell RA, Moran TM. TLR-independent induction of dendritic cell maturation and adaptive immunity by negative-strand 155 RNA viruses. J Immunol 2004; 173:6882-9.
55. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T. The RNA helicase RIG-I has an essential function in doublestranded RNA-induced innate antiviral responses. Nat Immunol 2004;5:730-7.
56. Yoneyama M, Fujita T. RIG-I family RNA helicases: cytoplasmic sensor for antiviral innate immunity. Cytokine Growth Factor Rev 2007;18:545-51.
57. Yoneyama M, Fujita T. Function of RIG-I-like receptors in antiviral innate immunity. J Biol Chern 2007;282:15315-8.
58. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M Jr, Akira S, Yonebara S, Kato A, Fujita T. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 2005; 175:2851-8.
59. Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T, Lu Y, Miyagishi M, Kodama T, Honda K, Ohba Y, Taniguchi T. DAI (DLM-lIZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 2007;448:501-5.
60. Sumpter R Jr, Loo YM, Foy E, Li K, Yoneyama M, Fujita T, Lemon SM, Gale M Jr. Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. J Virol 2005;79:2689-99
61. Cheng G, Zhong J, Chung J, Chisari FV Double-stranded DNA and double-stranded RNA induce a common antiviral signaling pathway in human cells. Proc Natl Acad Sci USA 2007;104:9035-40.
62. Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P, Weber F, Reis e Sousa C. RIG-I-mediated antiviral responses to single-strandedRNA bearing 5'-phosphates. Science 2006; 314:997-1001.
63. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006; 441:101-5.
64. Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, Tsujirnura T, Takeda K, Fujita T, Takeuchi O, Akira S. Cell type-specific involvement of RIG-I in antiviral response. Immunity 2005;23:19-28.
65. Loo YM, Fomek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill MA, Garcia-Sastre A, Katze MG, Gale M Jr. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 2008;82:335-45.
66. Takeuchi O, Akira S. MDA5/RIG-I and virus recognition. Curr Opin Immunol 2008;20:17-22.
67. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S. IPS-I, an adaptor triggering RIG-I- and Moo-mediated type I interferon induction. Nat Immunol 2005;6:981-8.
68. Meylan E, Curran J, Hofinann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J. Cardif is an adaptorprotein in the RIG-I antiviral pathway and is targeted by hepatitisC virus. Nature 2005;437:1167-72.
69. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 2005;122: 669-82.
70. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. VISAis an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 2005;19:727-40.
71. Kumar H, Kawai T, Kato H, Sato S, Takahashi K, Coban C, Yamamoto M, Uematsu S, Ishii KJ, Takeuchi O, Akira S. Essential role of IPS-l in innate immune responses against RNA viruses. J ExpMed 2006;203: 1795-803.
72. Sun Q, Sun L, Liu HH, Chen X, Seth RB, Forman J, Chen ZJ. The specific and essential role of MAVS in antiviral innate immune responses. Immunity 2006;24:633-42.
73. Yoneyama M, Fujita T. Cytoplasmic double-stranded DNA sensor. Nat Immtmol 2007;8:907-8.
74. Ha SC, Kim D, Hwang HY, Rich A, Kim YG, Kim KK. The crystal structure of the second Z-DNA binding domain of human DAI (ZBP1) in complex with Z-DNA reveals an unusual binding mode to Z-DNA. Proc Natl Acad Sci USA 2008;105:20671-6.
75. Ramakrishnan V Ribosome structure and the mechanism of translation. Cell 2002;108:557-72.
76. Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann KK, Schlee M, Endres S, Hartmann G. 5'-Triphosphate RNA is the ligand for RIG-I. Science 2006;314:994-7.
77. Myong S, Cui S, Cornish PV; Kirchhofer A, Gack MU, Jung JU, Hopfner KP, Ha T. Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA. Science 2009;323:1070-4.
78. Cui S, Eisenacher K, Kirchhofer A, Brzozka K, Lammens A, Lammens K, Fujita T, Conzelmann KK, Krug A, Hopfner KP. The C-terminal regulatory domain is the RNA 5'triphosphate sensor of RIG-I. Mol Cell 2008;29:169-79.
79. Saito T, Hirai R, Loo YM, Owen O, Johnson CL, Sinha SC, Akira S, Fujita T, Gale M Jr. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci USA 2007;104:582-7.
80. Malathi K, Dong B, Gale M Jr., Silverman RH. Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 2007;448:816-9
81. Barton GM, Kagan JC, Medzhitov R. Intracellular localization of Toll-like receptor9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol 2006;7:49-56
82. Marshak-Rothstein A, Rifkin IR. Immunologically active autoantigens: therole of toll-like receptors in the development of chronic inflammatory disease. Annu Rev Immunol 2007; 25:419-4l
83. Johansson C, Wetzel JD, He J, Mikacenic C, Dermody TS, Kelsall BL. Type I interferons produced by hematopoietic cells protect mice against lethal infection by mammalian reovirus. J Exp Med 2007;204: 1349-58.
84. Gowen B B, Hoopes J D, Wong M H, Jung KH, Isakson K C, Alexopoulou L, Flavell RA, Sidwell RW. TLR3 deletion limits mortality and disease severity due to Phlebovirus infection. J Immunol 2006;177:6301-7.
85. Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med 2004;10:1366-73.
86. Tabeta K, George P, Janssen E, Du X, Hoebe K, Crozat K, Mudd S, Shamel L, Sovath S, Goode J, Alexopoulou L, Flavell RA, Beutler B. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci USA 2004;101: 3516-21.
87. Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, Segalo D, Sancho-Shimizu V; Lorenzo L, Puel A, Picard C, Chapgier A, Plancoulaine S, Titeux M, Cognet C, von Bemuth H, Ku CL, Casrouge A, Zhang XX, Barreiro L, Leonard J, Hamilton C, Lebon P, Heron B, Vallee L, Quintana-Murci L, Hovnanian A, Rozenberg F, Vivier E, Geissmann F, Tardieu M, Abel L, Casanova JL. TLR3 deficiency in patients with herpes simplex encephalitis. Science 2007;317:1522-7.
88. Bochud PY, Magaret AS, Koelle DM, Aderem A, Wald A. Polymorphisms in TLR2 are associated with increased viral shedding and lesional rate in patients with genital herpes simplex virus type 2 infection. J Infect Dis 2007;196:505-9.
89. Finlay B.B, McFadden G. Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 2006;124:767-82.
90. Pichlmair A, Reis e Sousa C. Innate recognition of viruses. Immunity 2007;27:370-83.
91. Roy CR, Mocarski ES. Pathogen subversion of cell-intrinsic innate immunity. Nat Immunol 2007;8: 1179-87.
92. Diebold SS, Montoya M, Unger H, Alexopoulou L, Roy P, Haswell LE, AI-Shamkhani A, Flavell R, Borrow P, C Reis e Sousa C. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 2003;424:324-8.
93. Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the lFN-beta promoter. Proc Natl Acad Sci USA 2004;101:17264-9.
94. Stack J, Haga I.R, Schroder M, Bartlett N.W, Maloney G, Reading PC, Fitzgerald KA, Smith GL, Bowie AG. Vaccinia virus protein A46R targets multiple Toll-like-interleukin-I receptor adaptors and contributes to virulence. J Exp Med 2005;201: 1007-18.
95. Li XD, Sun L, Seth RB, Pineda G, Chen ZJ Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA 2005;102:17717-22.
96. Loo YM, Owen DM, Li K, Erickson AK, Johnson CL, Fish PM, Carney DS, Wang T, Ishida H, Yoneyama M, Fujita T, Saito T, Lee WM, Hagedorn CH, Lau DT, Weinman SA, Lemon SM, Gale M Jr. Viral and therapeutic control of lFN-beta promoter stimulator 1 during hepatitis C virus infection. Proc Natl Acad Sci USA 2006; 103:6001-6.
97. Fenster V, Grotheer D, Berk I, Schlemminger S, Vallbracht A, Dotzauer A. Hepatitis A virus suppresses RIG-I-mediated IRF-3 activation to block induction of beta interferon. J Virol 2005;79: 10968-77.
98. Yang Y, Liang Y, Qu L, Chen Z, Yi M, Li K, Lemon SM. Disruption of innate immunity due to mitochondrial targeting of a picomaviral protease precursor. Proc Natl Acad Sci USA 2007;104:7253-8.
99. Krieg AM, Wu T, Weeratna R, Etler SM, Love-Homan L, Yang L, Yi AK, Short D, Davis HL. Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs. Proc Natl Acad Sci USA 1998;95:12631-6.
100. Palm NW, Medzhitov R. Not so fast: adaptive suppression of innate immunity. Nat Med 2007;13:1142-4.
101. Kim KD, Zhao J, Auh S, Yang X, Du P, Tang H, Fu YX. Adaptive immune cells temper initial innate responses. Nat Med 2007;13:1248-52.