RNA recognition in immune cells

RNA stellt einen Stimulus für das angeborene Immunsystem durch die Aktivierung der endosomalen TLRs (3, 7 und 8) oder der zytosolischen RNA Sensoren (RIG-I und MDA-5) dar. Die Erkennung von RNA resultiert in der Sekretion von Typ-I Interferonen und / oder proinflammatorischen Zytokinen. Fremd-RNA wi...

Ausführliche Beschreibung

Gespeichert in:
1. Verfasser: von Thülen, Tina
Beteiligte: Bauer, Stefan (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2010
Allgemeinmedizin
Schlagworte:
Online Zugang:PDF-Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!

1. http://archiv.ub.uni-marburg.de/diss/z2006/0096


2. Hausmann, S., J. B. Marq, et al. (2008). "RIG-I and dsRNA-induced IFNbeta activation." PLoS One 3(12): e3965.


3. Matlin, K. S. and K. Simons (1984). "Sorting of an apical plasma membrane glycoprotein occurs before it reaches the cell surface in cultured epithelial cells." J Cell Biol 99(6): 2131-9.


4. De Jong, J. C. I. E. P., G. F. Rimmelzwaan, et al. (2000). "Influenza virus: a master of metamorphosis." J Infect 40(3): 218-28.


5. Dorschner, R. A. L.-K., V. K. Pestonjamasp, et al. (2001). "Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus." J Invest Dermatol 117(1): 91-7.


6. Thompson, J. E., F. D. Venegas, et al. (1994). "Energetics of catalysis by ribonucleases: fate of the 2',3'-cyclic phosphodiester intermediate." Biochemistry 33(23): 7408-14.


7. Flamand, L. O. L.-L. B., M. J. Tremblay, et al. (2007). "Leukotriene B4 triggers the in vitro and in vivo release of potent antimicrobial agents." J Immunol 178(12): 8036-45.


8. Martinon, F. (2008). "Detection of immune danger signals by NALP3." J Leukoc Biol 83(3): 507-11.


9. Pertzev, A. V. and A. W. Nicholson (2006). "Characterization of RNA sequence determinants and antideterminants of processing reactivity for a minimal substrate of Escherichia coli ribonuclease III." Nucleic Acids Res 34(13): 3708-21.


10. Janeway, C. A., Travers, P., Walport, M. (2005). Immunobiology, the immune system in health and disease, 6th edition


11. Rigby, R. E., A. Leitch, et al. (2008). "Nucleic acid-mediated inflammatory diseases." Bioessays 30(9): 833-42.


12. Scheel, B. V., S. Aulwurm, et al. (2006). "Therapeutic anti-tumor immunity triggered by injections of immunostimulating single-stranded RNA." Eur J Immunol 36(10): 2807-16.


13. Rehwinkel, J., C. P. Tan, et al. (2010). "RIG-I Detects Viral Genomic RNA during Negative-Strand RNA Virus Infection." Cell 140(3): 397-408.


14. Hamm, S., E. Latz, et al. (2009). "Alternating 2'-O-ribose methylation is a universal approach for generating non-stimulatory siRNA by acting as TLR7 antagonist." Immunobiology.


15. Ishikawa, H., Z. Ma, et al. (2009). "STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity." Nature.


16. Gilliet, M. o. D., W. Cao, et al. (2008). "Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases." Nat Rev Immunol 8(8): 594-606.


17. Hamm, S. O. I. V., A. Heit, et al. (2007). "Immunostimulatory RNA is a potent inducer of antigen-specific cytotoxic and humoral immune response in vivo." Int Immunol 19(3): 297-304.


18. Tluk, S., M. Jurk, et al. (2009). "Sequences derived from self-RNA containing certain natural modifications act as suppressors of RNA-mediated inflammatory immune responses." Int Immunol 21(5): 607-19.


19. Wreschner, D. H., T. C. James, et al. (1981). "Ribosomal RNA cleavage, nuclease activation and 2-5A(ppp(A2'p)nA) in interferon-treated cells." Nucleic Acids Res 9(7): 1571-81.


20. Wang, Q., T. Niittymaki, et al. (2007). "Metal ion promoted cleavage of RNA phosphodiester bonds: from Zn(II) aqua ion to artificial ribonucleases." Nucleic Acids Symp Ser (Oxf)(51): 65-6.


21. Rehwinkel, J. and C. Reis e Sousa (2010). "RIGorous detection: exposing virus through RNA sensing." Science 327(5963): 284-6.


22. Gaudreault, E. and J. Gosselin (2008). "Leukotriene B4 induces release of antimicrobial peptides in lungs of virally infected mice." J Immunol 180(9): 6211-21.


23. Gaush, C. R., W. L. Hard, et al. (1966). "Characterization of an established line of canine kidney cells (MDCK)." Proc Soc Exp Biol Med 122(3): 931-5.


24. Kiss, T. (2001). "Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs." Embo J 20(14): 3617-22.


25. Hale, B. G., R. E. Randall, et al. (2008). "The multifunctional NS1 protein of influenza A viruses." J Gen Virol 89(Pt 10): 2359-76.


26. Gallo, R. L. O. L.-C., K. J. Kim, et al. (1997). "Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse." J Biol Chem 272(20): 13088-93.


27. Kanneganti, T. D., N. Ozoren, et al. (2006). "Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3." Nature 440(7081): 233-6.


28. Thomas, P. G., P. Dash, et al. (2009). "The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1." Immunity 30(4): 566-75.


29. Aksoy, E. O. R., C. S. Zouain, et al. (2005). "Double-stranded RNAs from the helminth parasite Schistosoma activate TLR3 in dendritic cells." J Biol Chem 280(1): 277- 83.


30. Garcia, M., Z. Dogusan, et al. (2009). "Regulation and function of the cytosolic viral RNA sensor RIG-I in pancreatic beta cells." Biochim Biophys Acta.


31. Figdor, C. G., J. M. Leemans, et al. (1983). "Theory and practice of centrifugal elutriation (CE). Factors influencing the separation of human blood cells." Cell Biophys 5(2): 105-18.


32. Meylan, E. R.-I. M. I., J. Curran, et al. (2005). "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus." Nature 437(7062): 1167-72.


33. Ablasser, A., F. Bauernfeind, et al. (2009). "RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate." Nat Immunol.


34. Diebold, S. S. T., T. Kaisho, et al. (2004). "Innate antiviral responses by means of TLR7- mediated recognition of single-stranded RNA." Science 303(5663): 1529-31.


35. Diebold, S. S. O. T., C. Massacrier, et al. (2006). "Nucleic acid agonists for Toll-like receptor 7 are defined by the presence of uridine ribonucleotides." Eur J Immunol 36(12): 3256-67.


36. Robbins, M. s. R., A. Judge, et al. (2007). "2'-O-methyl-modified RNAs act as TLR7 antagonists." Mol Ther 15(9): 1663-9.


37. Barchet, W. O. T., V. Wimmenauer, et al. (2008). "Accessing the therapeutic potential of immunostimulatory nucleic acids." Curr Opin Immunol 20(4): 389-95.


38. Edy, V. G., M. Szekely, et al. (1976). "Action of nucleases on double-stranded RNA." Eur J Biochem 61(2): 563-72.


39. Eberle, F., 2009. Activation of Innate Immunity by Ribonucleic Acids.


40. Pichlmair, A., O. Schulz, et al. (2009). "Activation of MDA5 requires higher order RNA structures generated during virus infection." J Virol.


41. Dalby, B., S. Cates, et al. (2004). "Advanced transfection with Lipofectamine 2000 reagent: primary neurons, siRNA, and high-throughput applications." Methods 33(2): 95-103.


42. Kumagai, Y., O. Takeuchi, et al. (2007). "Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses." Immunity 27(2): 240-52.


43. Nestle, M. and W. K. Roberts (1969). "An extracellular nuclease from Serratia marcescens. II. Specificity of the enzyme." J Biol Chem 244(19): 5219-25.


44. Elssner, A. O. L.-P. X., M. Duncan, et al. (2004). "A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release." J Immunol 172(8): 4987-94.


45. Zaiou, M. O. L.-C. P., V. Nizet, et al. (2003). "Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence." J Invest Dermatol 120(5): 810-6.


46. Gilliet, M. O. L. and R. Lande (2008). "Antimicrobial peptides and self-DNA in autoimmune skin inflammation." Curr Opin Immunol 20(4): 401-407.


47. Brogden, K. A. O. L.-A. P. (2005). "Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?" Nat Rev Microbiol 3(3): 238-50.


48. Seth, R. B. O. v. r., L. Sun, et al. (2006). "Antiviral innate immunity pathways." Cell Res 16(2): 141-7.


49. Wang, Y. O. L.-L., B. Agerberth, et al. (1998). "Apolipoprotein A-I binds and inhibits the human antibacterial/cytotoxic peptide LL-37." J Biol Chem 273(50): 33115-8.


50. Schlee, M., E. Hartmann, et al. (2009). "Approaching the RNA ligand for RIG-I?" Immunol Rev 227(1): 66-74.


51. Gan, J., G. Shaw, et al. (2008). "A stepwise model for double-stranded RNA processing by ribonuclease III." Mol Microbiol 67(1): 143-54.


52. Ishii, K. J. O. D., C. Coban, et al. (2006). "A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA." Nat Immunol 7(1): 40-8.


53. Hemmi, H. O. T., O. Takeuchi, et al. (2000). "A Toll-like receptor recognizes bacterial DNA." Nature 408(6813): 740-5.


54. Baumgarth, N. and C. L. Bevins (2007). "Autoimmune disease: skin deep but complex." Nature 449(7162): 551-3.


55. Ahmad-Nejad, P., H. Hacker, et al. (2002). "Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments." Eur J Immunol 32(7): 1958-68.


56. Eberle, F., M. Sirin, et al. (2009). "Bacterial RNA is recognized by different sets of immunoreceptors." Eur J Immunol 39(9): 2537-47.


57. Tsurui, H., Y. Kumazawa, et al. (1994). "Batchwise purification of specific tRNAs by a solid-phase DNA probe." Anal Biochem 221(1): 166-72.


58. Ting, J. P. and B. K. Davis (2005). "CATERPILLER: a novel gene family important in immunity, cell death, and diseases." Annu Rev Immunol 23: 387-414.


59. Nagaoka, I., S. Hirota, et al. (2001). "Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells." J Immunol 167(6): 3329-38.


60. Zaiou, M. O. L.-L. a. and R. L. Gallo (2002). "Cathelicidins, essential gene-encoded mammalian antibiotics." J Mol Med 80(9): 549-61.


61. Ramanathan, B. L.-A. P., E. G. Davis, et al. (2002). "Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity." Microbes Infect 4(3): 361-72.


62. Zanetti, M. O. L.-L. a. (2004). "Cathelicidins, multifunctional peptides of the innate immunity." J Leukoc Biol 75(1): 39-48.


63. Almofti, M. R., H. Harashima, et al. (2003). "Cationic liposome-mediated gene delivery: biophysical study and mechanism of internalization." Arch Biochem Biophys 410(2): 246-53.


64. Pauligk, C. I. G., M. Nain, et al. (2004). "CD14 is required for influenza A virus-induced cytokine and chemokine production." Immunobiology 209(1-2): 3-10.


65. Kato, H. o. R.-I., S. Sato, et al. (2005). "Cell type-specific involvement of RIG-I in antiviral response." Immunity 23(1): 19-28.


66. Abbas, A. K., Lichtman, A. H., Pallai, S. (2007). Cellular and Molecular Immunology, 6th edition.


67. Gürtler, C., 2008. Charakterisierung der immunologischen Funktion der adenosine deaminase acting on RNA 1 (ADAR1).


68. Johansson, J. O. L.-I. i., G. H. Gudmundsson, et al. (1998). "Conformation-dependent antibacterial activity of the naturally occurring human peptide LL-37." J Biol Chem 273(6): 3718-24.


69. Lipford, G. B., T. Sparwasser, et al. (2000). "CpG-DNA-mediated transient lymphadenopathy is associated with a state of Th1 predisposition to antigen-driven responses." J Immunol 165(3): 1228-35.


70. Yasuda, K., M. Rutz, et al. (2006). "CpG motif-independent activation of TLR9 upon endosomal translocation of "natural" phosphodiester DNA." Eur J Immunol 36(2): 431-6.


71. Krieg, A. M. O. C. (2002). "CpG motifs in bacterial DNA and their immune effects." Annu Rev Immunol 20: 709-60.


72. Krieg, A. M., A. K. Yi, et al. (1995). "CpG motifs in bacterial DNA trigger direct B-cell activation." Nature 374(6522): 546-9.


73. Yusupov, M. M., G. Z. Yusupova, et al. (2001). "Crystal structure of the ribosome at 5.5 A resolution." Science 292(5518): 883-96.


74. Le Goffic, R. O. T. T. R., J. Pothlichet, et al. (2007). "Cutting Edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells." J Immunol 178(6): 3368-72.


75. Kumagai, Y., H. Kumar, et al. (2009). "Cutting Edge: TLR-Dependent viral recognition along with type I IFN positive feedback signaling masks the requirement of viral replication for IFN-{alpha} production in plasmacytoid dendritic cells." J Immunol 182(7): 3960-4.


76. Langlois, M. A., C. Boniface, et al. (2005). "Cytoplasmic and nuclear retained DMPK mRNAs are targets for RNA interference in myotonic dystrophy cells." J Biol Chem 280(17): 16949-54.


77. Takaoka, A. O. D., Z. Wang, et al. (2007). "DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response." Nature 448(7152): 501-5.


78. Kaufmann, A., R. Salentin, et al. (2001). "Defense against influenza A virus infection: essential role of the chemokine system." Immunobiology 204(5): 603-13.


79. Barchet, W., A. Krug, et al. (2005). "Dendritic cells respond to influenza virus through TLR7-and PKR-independent pathways." Eur J Immunol 35(1): 236-42.


80. Judge, A. D., G. Bola, et al. (2006). "Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo." Mol Ther 13(3): 494-505.


81. Bonin, M., J. Oberstrass, et al. (2000). "Determination of preferential binding sites for anti- dsRNA antibodies on double-stranded RNA by scanning force microscopy." Rna 6(4): 563-70.


82. Koyama, S., K. J. Ishii, et al. (2007). "Differential role of TLR-and RLR-signaling in the immune responses to influenza A virus infection and vaccination." J Immunol 179(7): 4711-20.


83. Kato, H. O. R.-I., O. Takeuchi, et al. (2006). "Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses." Nature 441(7089): 101-5.


84. McCartney, S., W. Vermi, et al. (2009). "Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells." J Exp Med 206(13): 2967-76.


85. Doctoral thesis


86. Edelmann, K. H. O. I. R.-M. T., S. Richardson-Burns, et al. (2004). "Does Toll-like receptor 3 play a biological role in virus infections?" Virology 322(2): 231-8.


87. Libonati, M., A. Carsana, et al. (1980). "Double-stranded RNA." Mol Cell Biochem 31(3): 147-64.


88. Weber, F. d. s. R., V. Wagner, et al. (2006). "Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses." J Virol 80(10): 5059-64.


89. Yashiro, M., M. Higuchi, et al. (2002). "Effect of Alkaline Earth Metal Ions on the Phisphodiester Hydrolysis of RNA." Bull. Chem. Soc. Jpn. 75: 1843-1844.


90. Edy, V. G., M. Szekely, et al. (1974). "Effect of fragmentation on interferon induction by double-stranded virus RNA." J Gen Virol 23(2): 191-5.


91. Meidan, V. M., D. Dunnion, et al. (1997). "Effect of ultrasound on the stability of oligonucleotides in vitro." International Journal of Pharmaceutics 152: 121-125.


92. Balachandran, S., P. C. Roberts, et al. (2000). "Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection." Immunity 13(1): 129-41.


93. Yasin, B. s. s., M. Pang, et al. (2000). "Evaluation of the inactivation of infectious Herpes simplex virus by host-defense peptides." Eur J Clin Microbiol Infect Dis 19(3): 187- 94.


94. Owen, D. M. and M. Gale, Jr. (2009). "Fighting the flu with inflammasome signaling." Immunity 30(4): 476-8.


95. McCall, K. A., C. Huang, et al. (2000). "Function and mechanism of zinc metalloenzymes." J Nutr 130(5S Suppl): 1437S-46S.


96. Nicholson, A. W. (1999). "Function, mechanism and regulation of bacterial ribonucleases." FEMS Microbiol Rev 23(3): 371-90.


97. Cekaite, L., G. Furset, et al. (2007). "Gene expression analysis in blood cells in response to unmodified and 2'-modified siRNAs reveals TLR-dependent and independent effects." J Mol Biol 365(1): 90-108.


98. Bachellerie, J. P. and J. Cavaille (1997). "Guiding ribose methylation of rRNA." Trends Biochem Sci 22(7): 257-61.


99. Hartmann, R. K., A. Bindereif , et al. (2005). "Handbook of RNA Biochemistry." Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


100. Krug, A., G. D. Luker, et al. (2004). "Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9." Blood 103(4): 1433-7.


101. Hochrein, H. v. r. a. I. i., B. Schlatter, et al. (2004). "Herpes simplex virus type-1 induces IFN-alpha production via Toll-like receptor 9-dependent and -independent pathways." Proc Natl Acad Sci U S A 101(31): 11416-21.


102. Matsuo, M., T. Yokogawa, et al. (1995). "Highly specific and efficient cleavage of squid tRNA(Lys) catalyzed by magnesium ions." J Biol Chem 270(17): 10097-104.


103. Hansmann, L., S. Groeger, et al. (2008). "Human monocytes represent a competitive source of interferon-alpha in peripheral blood." Clin Immunol 127(2): 252-64.


104. Jurk, M. T., F. Heil, et al. (2002). "Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848." Nat Immunol 3(6): 499.


105. Kurz, K. (1998). "Hydrolytische Spaltung von Nucleinsäuren-vom Enzymmechanismus zum Enzymmodell." Chemie in unserer Zeit, Wiley-VCH Verlag GmbH, 69469 Weinheim: 94-103.


106. Seth, R. B. O. R.-I., L. Sun, et al. (2005). "Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3." Cell 122(5): 669-82.


107. Opitz, B. I. I., A. Rejaibi, et al. (2007). "IFNbeta induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein." Cell Microbiol 9(4): 930-8.


108. Vollmer, J., S. Tluk, et al. (2005). "Immune stimulation mediated by autoantigen binding sites within small nuclear RNAs involves Toll-like receptors 7 and 8." J Exp Med 202(11): 1575-85.


109. Westwood, A., S. J. Elvin, et al. (2006). "Immunological responses after immunisation of mice with microparticles containing antigen and single stranded RNA (polyuridylic acid)." Vaccine 24(11): 1736-43.


110. Scheel, B., S. Braedel, et al. (2004). "Immunostimulating capacities of stabilized RNA molecules." Eur J Immunol 34(2): 537-47.


111. Gack, M. U., R. A. Albrecht, et al. (2009). "Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I." Cell Host Microbe 5(5): 439-49.


112. Rotem, Z., R. A. Cox, et al. (1963). "Inhibition of virus multiplication by foreign nucleic acid." Nature 197: 564-6.


113. Dorschner, R. A., B. Lopez-Garcia, et al. (2004). "Innate immune defense of the nail unit by antimicrobial peptides." J Am Acad Dermatol 50(3): 343-8.


114. Janeway, C. A., Jr. ordner allgemein and R. Medzhitov (2002). "Innate immune recognition." Annu Rev Immunol 20: 197-216.


115. Saito, T. R. I. M. I., D. M. Owen, et al. (2008). "Innate immunity induced by composition- dependent RIG-I recognition of hepatitis C virus RNA." Nature 454(7203): 523-7.


116. Bals, R. O. L.-B. and P. S. Hiemstra (2004). "Innate immunity in the lung: how epithelial cells fight against respiratory pathogens." Eur Respir J 23(2): 327-33.


117. Pichlmair, A. V. r. and C. Reis e Sousa (2007). "Innate recognition of viruses." Immunity 27(3): 370-83.


118. Hornung, V. and E. Latz (2010). "Intracellular DNA recognition." Nat Rev Immunol 10(2): 123-30.


119. Barton, G. M. T., J. C. Kagan, et al. (2006). "Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA." Nat Immunol 7(1): 49-56.


120. Sun, W., E. Jun, et al. (2001). "Intrinsic double-stranded-RNA processing activity of Escherichia coli ribonuclease III lacking the dsRNA-binding domain." Biochemistry 40(49): 14976-84.


121. Wegscheid B., 2006. In vitro and in vivo investigations on the interaction of bacterial


122. Hoerr, I., R. Obst, et al. (2000). "In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies." Eur J Immunol 30(1): 1-7.


123. Guillot, L. I. T. M. R., R. Le Goffic, et al. (2005). "Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus." J Biol Chem 280(7): 5571-80.


124. Liu, Y. J. O. D. (2005). "IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors." Annu Rev Immunol 23: 275-306.


125. Kawai, T. R. I. M. I., K. Takahashi, et al. (2005). "IPS-1, an adaptor triggering RIG-I-and Mda5-mediated type I interferon induction." Nat Immunol 6(10): 981-8.


126. Eaves, G. N. and C. D. Jeffries (1963). "Isolation and Properties of an Exocellular Nuclease of Serratia Marcescens." J Bacteriol 85(2): 273-8.


127. Kato, H. O. R.-I., O. Takeuchi, et al. (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(7): 1601-10.


128. Satoh, T., H. Kato, et al. (2010). "LGP2 is a positive regulator of RIG-I-and MDA5- mediated antiviral responses." Proc Natl Acad Sci U S A 107(4): 1512-7.


129. De, Y. O. L.-O. F., Q. Chen, et al. (2000). "LL-37, the neutrophil granule-and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells." J Exp Med 192(7): 1069-74.


130. Durr, U. H. O. L.-L. a., U. S. Sudheendra, et al. (2006). "LL-37, the only human member of the cathelicidin family of antimicrobial peptides." Biochim Biophys Acta 1758(9): 1408-25.


131. Fancke, B., M. Suter, et al. (2008). "M-CSF: a novel plasmacytoid and conventional dendritic cell poietin." Blood 111(1): 150-9.


132. Takeuchi, O. O. v. r. a. I. and S. Akira (2008). "MDA5/RIG-I and virus recognition." Curr Opin Immunol 20(1): 17-22.


133. Xu, Y. O. D. and F. C. Szoka, Jr. (1996). "Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection." Biochemistry 35(18): 5616-23.


134. Eberle, F., K. Giessler, et al. (2008). "Modifications in small interfering RNA that separate immunostimulation from RNA interference." J Immunol 180(5): 3229-37.


135. Mookherjee, N. O. L.-I. f. o. T., K. L. Brown, et al. (2006). "Modulation of the TLR- mediated inflammatory response by the endogenous human host defense peptide LL-37." J Immunol 176(4): 2455-64.


136. Pauglik, C., 2002. Molekulare Wechselwirkungen zwischen Infleunza A-Viren und humanen Monozyten: Genregulation und Signalübertragung.


137. Kurosaka, K. O. L.-I., Q. Chen, et al. (2005). "Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant." J Immunol 174(10): 6257-65.


138. Yang, D. O. L.-A. P., A. Biragyn, et al. (2004). "Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense." Annu Rev Immunol 22: 181-215.


139. Martinon, F., O. Gaide, et al. (2007). "NALP inflammasomes: a central role in innate immunity." Semin Immunopathol 29(3): 213-29.


140. Tschopp, J., F. Martinon, et al. (2003). "NALPs: a novel protein family involved in inflammation." Nat Rev Mol Cell Biol 4(2): 95-104.


141. Arnold, U. and R. Ulbrich-Hofmann (2006). "Natural and engineered ribonucleases as potential cancer therapeutics." Biotechnol Lett 28(20): 1615-22.


142. Kariko, K. r. and D. Weissman (2007). "Naturally occurring nucleoside modifications suppress the immunostimulatory activity of RNA: implication for therapeutic RNA development." Curr Opin Drug Discov Devel 10(5): 523-32.


143. Gudmundsson, G. H. O. L.-a. P. and B. Agerberth (1999). "Neutrophil antibacterial peptides, multifunctional effector molecules in the mammalian immune system." J Immunol Methods 232(1-2): 45-54.


144. Cao, X. (2009). "New DNA-sensing pathway feeds RIG-I with RNA." Nat Immunol 10(10): 1049-51.


145. Guo, Z. I. N., L. M. Chen, et al. (2007). "NS1 protein of influenza A virus inhibits the function of intracytoplasmic pathogen sensor, RIG-I." Am J Respir Cell Mol Biol 36(3): 263-9.


146. Krug, A. S. (2008). "Nucleic acid recognition receptors in autoimmunity." Handb Exp Pharmacol(183): 129-51.


147. Lamb, R. A. and R. M. Krug (1996). "Orthomyxoviridae: The viruses and their replication." Field, B. N., Knipe, D.N., et al. (eds), Virology. Lippincott-Raven Publishers, Philadelphia. : 1353-1395.


148. Jenssen, H. O. L.-a. P., P. Hamill, et al. (2006). "Peptide antimicrobial agents." Clin Microbiol Rev 19(3): 491-511.


149. Termen, S., M. Tollin, et al. (2003). "Phylogeny, processing and expression of the rat cathelicidin rCRAMP: a model for innate antimicrobial peptides." Cell Mol Life Sci 60(3): 536-49.


150. Verdijk, R. M., T. Mutis, et al. (1999). "Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells." J Immunol 163(1): 57-61.


151. Jarrousse, A. S., F. Petit, et al. (1999). "Possible involvement of proteasomes (prosomes) in AUUUA-mediated mRNA decay." J Biol Chem 274(9): 5925-30.


152. Riedl, P., D. Stober, et al. (2002). "Priming Th1 immunity to viral core particles is facilitated by trace amounts of RNA bound to its arginine-rich domain." J Immunol 168(10): 4951-9.


153. Flint, S. J., L. W. Enquist, et al. (2004). "Princples of virology." American Society for Microbiology.


154. Horikoshi, T., J. Page, et al. (1998). "Proteasomal RNase activity in human epidermis." In Vivo 12(2): 155-8.


155. Petit, F., A. S. Jarrousse, et al. (1997). "Proteasome (prosome) associated endonuclease activity." Mol Biol Rep 24(1-2): 113-7.


156. Kirikae, T., M. Hirata, et al. (1998). "Protective effects of a human 18-kilodalton cationic antimicrobial protein (CAP18)-derived peptide against murine endotoxemia." Infect Immun 66(5): 1861-8.


157. Meador, J., 3rd, B. Cannon, et al. (1990). "Purification and characterization of Escherichia coli RNase I. Comparisons with RNase M." Eur J Biochem 187(3): 549-53.


158. Robertson, H. D., R. E. Webster, et al. (1968). "Purification and properties of ribonuclease III from Escherichia coli." J Biol Chem 243(1): 82-91.


159. Stetson, D. B. O. D. and R. Medzhitov (2006). "Recognition of cytosolic DNA activates an IRF3-dependent innate immune response." Immunity 24(1): 93-103.


160. Bauer, S., S. Pigisch, et al. (2008). "Recognition of nucleic acid and nucleic acid analogs by Toll-like receptors 7, 8 and 9." Immunobiology 213(3-4): 315-28.


161. Yoneyama, M. and T. Fujita (2010). "Recognition of viral nucleic acids in innate immunity." Rev Med Virol 20(1): 4-22.


162. Takeuchi, O. O. V. r. and S. Akira (2007). "Recognition of viruses by innate immunity." Immunol Rev 220: 214-24.


163. Siren, J. o. v. r. a., T. Imaizumi, et al. (2006). "Retinoic acid inducible gene-I and mda-5 are involved in influenza A virus-induced expression of antiviral cytokines." Microbes Infect 8(8): 2013-20.


164. Libonati, M. and S. Sorrentino (1992). "Revisiting the action of bovine ribonuclease A and pancreatic-type ribonucleases on double-stranded RNA." Mol Cell Biochem 117(2): 139-51.


165. Conrad, C. and R. Rauhut (2002). "Ribonuclease III: new sense from nuisance." Int J Biochem Cell Biol 34(2): 116-29.


166. Deshpande, R. A. and V. Shankar (2002). "Ribonucleases from T2 family." Crit Rev Microbiol 28(2): 79-122.


167. Pichlmair, A. O. R.-I., O. Schulz, et al. (2006). "RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates." Science 314(5801): 997-1001.


168. Decatur, W. A. and M. J. Fournier (2003). "RNA-guided nucleotide modification of ribosomal and other RNAs." J Biol Chem 278(2): 695-8.


169. Dunn, J. J. (1976). "RNase III cleavage of single-stranded RNA. Effect of ionic strength on the fideltiy of cleavage." J Biol Chem 251(12): 3807-14.


170. Carmell, M. A. O. R. and G. J. Hannon (2004). "RNase III enzymes and the initiation of gene silencing." Nat Struct Mol Biol 11(3): 214-8.


171. RNase P with tRNA 3`-CCA.


172. Czaja, R., M. Struhalla, et al. (2004). "RNase T1 variant RV cleaves single-stranded RNA after purines due to specific recognition by the Asn46 side chain amide." Biochemistry 43(10): 2854-62.


173. Howell, M. D. o. L.-V., J. F. Jones, et al. (2004). "Selective killing of vaccinia virus by LL- 37: implications for eczema vaccinatum." J Immunol 172(3): 1763-7.


174. Hornung, V. o. s., M. Guenthner-Biller, et al. (2005). "Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7." Nat Med 11(3): 263-70.


175. Yoneyama, M. O. R. I. a., M. Kikuchi, et al. (2005). "Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity." J Immunol 175(5): 2851-8.


176. Lee, M. S. T. and Y. J. Kim (2007). "Signaling pathways downstream of pattern- recognition receptors and their cross talk." Annu Rev Biochem 76: 447-80.


177. Sioud, M. (2006). "Single-stranded small interfering RNA are more immunostimulatory than their double-stranded counterparts: a central role for 2'-hydroxyl uridines in immune responses." Eur J Immunol 36(5): 1222-30.


178. Desai, N. A. and V. Shankar (2003). "Single-strand-specific nucleases." FEMS Microbiol Rev 26(5): 457-91.


179. Hemmi, H., T. Kaisho, et al. (2002). "Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway." Nat Immunol 3(2): 196-200.


180. Takahasi, K., H. Kumeta, et al. (2009). "Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I- like receptors." J Biol Chem 284(26): 17465-74.


181. Heil, F., H. Hemmi, et al. (2004). "Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8." Science 303(5663): 1526-9.


182. Probst, J. U. M., B. Weide, et al. (2007). "Spontaneous cellular uptake of exogenous messenger RNA in vivo is nucleic acid-specific, saturable and ion dependent." Gene Ther 14(15): 1175-80.


183. Majde, J. A., N. Guha-Thakurta, et al. (1998). "Spontaneous release of stable viral double- stranded RNA into the extracellular medium by influenza virus-infected MDCK epithelial cells: implications for the viral acute phase response." Arch Virol 143(12): 2371-80.


184. Leung, D. W., K. C. Prins, et al. (2010). "Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35." Nat Struct Mol Biol 17(2): 165-72.


185. Molhoek, E. M., A. L. den Hertog, et al. (2009). "Structure-function relationship of the human antimicrobial peptide LL-37 and LL-37 fragments in the modulation of TLR responses." Biol Chem.


186. Matsumoto, M., K. Funami, et al. (2003). "Subcellular localization of Toll-like receptor 3 in human dendritic cells." J Immunol 171(6): 3154-62.


187. Gautier-Bert, K., B. Murol, et al. (2003). "Substrate affinity and substrate specificity of proteasomes with RNase activity." Mol Biol Rep 30(1): 1-7.


188. Sioud, M., G. Furset, et al. (2007). "Suppression of immunostimulatory siRNA-driven innate immune activation by 2'-modified RNAs." Biochem Biophys Res Commun 361(1): 122-6.


189. Kariko, K. O. S. R., M. Buckstein, et al. (2005). "Suppression of RNA recognition by Toll- like receptors: the impact of nucleoside modification and the evolutionary origin of RNA." Immunity 23(2): 165-75.


190. Ronnblom, L. and G. V. Alm (2003). "Systemic lupus erythematosus and the type I interferon system." Arthritis Res Ther 5(2): 68-75.


191. Zhong, B. a., Y. Yang, et al. (2008). "The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation." Immunity 29(4): 538-50.


192. Bergman, P. n. z. l., L. Walter-Jallow, et al. (2007). "The antimicrobial peptide LL-37 inhibits HIV-1 replication." Curr HIV Res 5(4): 410-5.


193. Heilborn, J. D. O. L.-W., M. F. Nilsson, et al. (2003). "The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium." J Invest Dermatol 120(3): 379-89.


194. Davidson, D. J. O. L.-K., A. J. Currie, et al. (2004). "The cationic antimicrobial peptide LL- 37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization." J Immunol 172(2): 1146-56.


195. Cui, S. O. R.-I., K. Eisenacher, et al. (2008). "The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I." Mol Cell 29(2): 169-79.


196. Cordin, O., J. Banroques, et al. (2006). "The DEAD-box protein family of RNA helicases." Gene 367: 17-37.


197. Deddouche, S., N. Matt, et al. (2008). "The DExD/H-box helicase Dicer-2 mediates the induction of antiviral activity in drosophila." Nat Immunol 9(12): 1425-32.


198. Lemaitre, B. D., E. Nicolas, et al. (1996). "The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults." Cell 86(6): 973-83.


199. Bachellerie, J. P., J. Cavaille, et al. (2002). "The expanding snoRNA world." Biochimie 84(8): 775-90.


200. Frohm, M. O. L.-E., B. Agerberth, et al. (1997). "The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders." J Biol Chem 272(24): 15258-63.


201. Sorensen, O. O. L.-L., T. Bratt, et al. (1999). "The human antibacterial cathelicidin, hCAP- 18, is bound to lipoproteins in plasma." J Biol Chem 274(32): 22445-51.


202. Agerberth, B. O. L.-E., J. Charo, et al. (2000). "The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations." Blood 96(9): 3086-93.


203. Sandgren, S. O. L., A. Wittrup, et al. (2004). "The human antimicrobial peptide LL-37 transfers extracellular DNA plasmid to the nuclear compartment of mammalian cells via lipid rafts and proteoglycan-dependent endocytosis." J Biol Chem 279(17): 17951-6.


204. Gudmundsson, G. H. O. L.-L. a., B. Agerberth, et al. (1996). "The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes." Eur J Biochem 238(2): 325-32.


205. Afonina, E., R. Stauber, et al. (1998). "The human poly(A)-binding protein 1 shuttles between the nucleus and the cytoplasm." J Biol Chem 273(21): 13015-21.


206. Muruve, D. A. O. D., V. Petrilli, et al. (2008). "The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response." Nature 452(7183): 103-7.


207. Dorschner, R. A. O. L.-I. E., B. Lopez-Garcia, et al. (2006). "The mammalian ionic environment dictates microbial susceptibility to antimicrobial defense peptides." Faseb J 20(1): 35-42.


208. Maden, B. E. (1990). "The numerous modified nucleotides in eukaryotic ribosomal RNA." Prog Nucleic Acid Res Mol Biol 39: 241-303.


209. Pippig, D. A., J. C. Hellmuth, et al. (2009). "The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA." Nucleic Acids Res. Pouch, M. N., F. Petit, et al. (1995). "Identification and initial characterization of a specific proteasome (prosome) associated RNase activity." J Biol Chem 270(37): 22023-8.


210. Dyer, K. D. and H. F. Rosenberg (2006). "The RNase a superfamily: generation of diversity and innate host defense." Mol Divers 10(4): 585-97.


211. Cuchillo, C. M., X. Pares, et al. (1993). "The role of 2',3'-cyclic phosphodiesters in the bovine pancreatic ribonuclease A catalysed cleavage of RNA: intermediates or products?" FEBS Lett 333(3): 207-10.


212. Zanetti, M. O. L.-a. P. (2005). "The role of cathelicidins in the innate host defenses of mammals." Curr Issues Mol Biol 7(2): 179-96.


213. Drider, D., J. M. Santos, et al. (1999). "The role of Escherichia coli RNase E and RNase III in the processing of the citQRP operon mRNA from Lactococcus lactis biovar diacetylactis." J Mol Microbiol Biotechnol 1(2): 337-46.


214. Eisenacher, K., C. Steinberg, et al. (2007). "The role of viral nucleic acid recognition in dendritic cells for innate and adaptive antiviral immunity." Immunobiology 212(9- 10): 701-14.


215. Sun, Q. R. M. I., L. Sun, et al. (2006). "The specific and essential role of MAVS in antiviral innate immune responses." Immunity 24(5): 633-42.


216. Heil, F. O. T., P. Ahmad-Nejad, et al. (2003). "The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily." Eur J Immunol 33(11): 2987-97.


217. Papon, L., A. Oteiza, et al. (2009). "The viral RNA recognition sensor RIG-I is degraded during encephalomyocarditis virus (EMCV) infection." Virology.


218. Ishii, K. J. s. R. and S. Akira (2005). "TLR ignores methylated RNA?" Immunity 23(2): 111- 3.


219. Lopez, C. B., B. Moltedo, et al. (2004). "TLR-independent induction of dendritic cell maturation and adaptive immunity by negative-strand RNA viruses." J Immunol 173(11): 6882-9.


220. Boule, M. W., C. Broughton, et al. (2004). "Toll-like receptor 9-dependent and - independent dendritic cell activation by chromatin-immunoglobulin G complexes." J Exp Med 199(12): 1631-40.


221. Kawai, T. and S. Akira (2008). "Toll-like receptor and RIG-I-like receptor signaling." Ann N Y Acad Sci 1143: 1-20.


222. Iwasaki, A. and R. Medzhitov (2004). "Toll-like receptor control of the adaptive immune responses." Nat Immunol 5(10): 987-95.


223. Rifkin, I. R. A., E. A. Leadbetter, et al. (2005). "Toll-like receptors, endogenous ligands, and systemic autoimmune disease." Immunol Rev 204: 27-42.


224. Akira, S. O. T. and K. Takeda (2004). "Toll-like receptor signalling." Nat Rev Immunol 4(7): 499-511.


225. Uematsu, S. B. and S. Akira (2008). "Toll-Like receptors (TLRs) and their ligands." Handb Exp Pharmacol(183): 1-20.


226. Romoren, K. D., B. J. Thu, et al. (2004). "Transfection efficiency and cytotoxicity of cationic liposomes in salmonid cell lines of hepatocyte and macrophage origin." Biochim Biophys Acta 1663(1-2): 127-34.


227. Bals, R. O. L.-B., D. J. Weiner, et al. (1999). "Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model." J Clin Invest 103(8): 1113-7.


228. Pulendran, B. and R. Ahmed (2006). "Translating innate immunity into immunological memory: implications for vaccine development." Cell 124(4): 849-63.


229. Nain, M., F. Hinder, et al. (1990). "Tumor necrosis factor-alpha production of influenza A virus-infected macrophages and potentiating effect of lipopolysaccharides." J Immunol 145(6): 1921-8.


230. Banchereau, J. O. I. and V. Pascual (2006). "Type I interferon in systemic lupus erythematosus and other autoimmune diseases." Immunity 25(3): 383-92.


231. Theofilopoulos, A. N. O. A., R. Baccala, et al. (2005). "Type I interferons (alpha/beta) in immunity and autoimmunity." Annu Rev Immunol 23: 307-36.


232. Savarese, E., O. W. Chae, et al. (2006). "U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells through TLR7." Blood 107(8): 3229-34.


233. Elsner, H. I. and E. B. Lindblad (1989). "Ultrasonic degradation of DNA." DNA 8(10): 697- 701.


234. Majde, J. A. (2000). "Viral double-stranded RNA, cytokines, and the flu." J Interferon Cytokine Res 20(3): 259-72.


235. Silverman, R. H. (2007). "Viral encounters with 2',5'-oligoadenylate synthetase and RNase L during the interferon antiviral response." J Virol 81(23): 12720-9.


236. McCartney, S. A. and M. Colonna (2009). "Viral sensors: diversity in pathogen recognition." Immunol Rev 227(1): 87-94.


237. Xu, L. G. R.-I. M. I., Y. Y. Wang, et al. (2005). "VISA is an adapter protein required for virus-triggered IFN-beta signaling." Mol Cell 19(6): 727-40.


238. Sorensen, O. E. L.-.-P., P. Follin, et al. (2001). "Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3." Blood 97(12): 3951-9.


239. Schlee, M., A. Roth, et al. (2009). "Recognition of 5' triphosphate by RIG-I helicase requires short blunt double-stranded RNA as contained in panhandle of negative- strand virus." Immunity 31(1): 25-34.


240. Bals, R. O. L.-B. (2000). "Epithelial antimicrobial peptides in host defense against infection." Respir Res 1(3): 141-50.


241. Raines, R. T. (1998). "Ribonuclease A." Chem Rev 98(3): 1045-1066.


242. Rothenfusser, S. O. R. I. L., N. Goutagny, et al. (2005). "The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I." J Immunol 175(8): 5260-8.


243. Brydon, E. W. I. A., S. J. Morris, et al. (2005). "Role of apoptosis and cytokines in influenza virus morbidity." FEMS Microbiol Rev 29(4): 837-50.


244. Probst, J., S. Brechtel, et al. (2006). "Characterization of the ribonuclease activity on the skin surface." Genet Vaccines Ther 4: 4.


245. Kariko, K. O. s. R., H. Ni, et al. (2004). "mRNA is an endogenous ligand for Toll-like receptor 3." J Biol Chem 279(13): 12542-50.


246. Yasuda, K. O. D., P. Yu, et al. (2005). "Endosomal translocation of vertebrate DNA activates dendritic cells via TLR9-dependent and -independent pathways." J Immunol 174(10): 6129-36.


247. Crow, Y. J., A. Leitch, et al. (2006). "Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection." Nat Genet 38(8): 910-6.


248. Alexopoulou, L. O. T., A. C. Holt, et al. (2001). "Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3." Nature 413(6857): 732-8.


249. Zasloff, M. o. L.-a. P. (2002). "Antimicrobial peptides of multicellular organisms." Nature 415(6870): 389-95.


250. Yoneyama, M. o. R., M. Kikuchi, et al. (2004). "The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses." Nat Immunol 5(7): 730-7.


251. Turner, J. O. L.-L. a., Y. Cho, et al. (1998). "Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils." Antimicrob Agents Chemother 42(9): 2206-14.


252. Garcia-Sastre, A. I. I., R. K. Durbin, et al. (1998). "The role of interferon in influenza virus tissue tropism." J Virol 72(11): 8550-8.


253. Bergmann, M., A. Garcia-Sastre, et al. (2000). "Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication." J Virol 74(13): 6203-6.


254. Kiss-Laszlo, Z., Y. Henry, et al. (1998). "Sequence and structural elements of methylation guide snoRNAs essential for site-specific ribose methylation of pre-rRNA." Embo J 17(3): 797-807.


255. Petit, F., A. S. Jarrousse, et al. (1997). "Involvement of proteasomal subunits zeta and iota in RNA degradation." Biochem J 326 ( Pt 1): 93-8.


256. Min, J. Y. and R. M. Krug (2006). "The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: Inhibiting the 2'-5' oligo (A) synthetase/RNase L pathway." Proc Natl Acad Sci U S A 103(18): 7100-5.


257. Gitlin, L. O. R. M., W. Barchet, et al. (2006). "Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus." Proc Natl Acad Sci U S A 103(22): 8459-64.


258. Cirioni, O. O. L.-K., A. Giacometti, et al. (2006). "LL-37 protects rats against lethal sepsis caused by gram-negative bacteria." Antimicrob Agents Chemother 50(5): 1672-9.


259. Koczulla, R. O. L.-B., G. von Degenfeld, et al. (2003). "An angiogenic role for the human peptide antibiotic LL-37/hCAP-18." J Clin Invest 111(11): 1665-72.


260. Czauderna, F., M. Fechtner, et al. (2003). "Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells." Nucleic Acids Res 31(11): 2705-16.


261. Lee, J., T. H. Chuang, et al. (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(11): 6646-51.


262. Larrick, J. W. O. L.-S., M. Hirata, et al. (1995). "Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein." Infect Immun 63(4): 1291-7.


263. Saito, T., R. Hirai, et al. (2007). "Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2." Proc Natl Acad Sci U S A 104(2): 582-7.


264. Mibayashi, M., L. Martinez-Sobrido, et al. (2007). "Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus." J Virol 81(2): 514-24.


265. Silverman, R. H. (2007). "A scientific journey through the 2-5A/RNase L system." Cytokine Growth Factor Rev 18(5-6): 381-8.


266. Cereijido, M., E. S. Robbins, et al. (1978). "Polarized monolayers formed by epithelial cells on a permeable and translucent support." J Cell Biol 77(3): 853-80.


267. Kumar, H. O. R.-I., T. Kawai, et al. (2006). "Essential role of IPS-1 in innate immune responses against RNA viruses." J Exp Med 203(7): 1795-803.


268. Bals, R. O. L.-B., X. Wang, et al. (1998). "The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface." Proc Natl Acad Sci U S A 95(16): 9541-6.


269. Leber, J. H., G. T. Crimmins, et al. (2008). "Distinct TLR-and NLR-mediated transcriptional responses to an intracellular pathogen." PLoS Pathog 4(1): e6.


270. Barrat, F. J., T. Meeker, et al. (2005). "Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus." J Exp Med 202(8): 1131-9.


271. Loo, Y. M. O. v. r. a. I., J. Fornek, et al. (2008). "Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity." J Virol 82(1): 335-45.


272. Kim, M. J., S. Y. Hwang, et al. (2008). "Negative feedback regulation of RIG-I-mediated antiviral signaling by interferon-induced ISG15 conjugation." J Virol 82(3): 1474-83.


273. Fitzgerald-Bocarsly, P., J. Dai, et al. (2008). "Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history." Cytokine Growth Factor Rev 19(1): 3-19.


274. Habjan, M. o. v. r., I. Andersson, et al. (2008). "Processing of genome 5' termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction." PLoS ONE 3(4): e2032.


275. Saito, T. O. R.-I. and M. Gale, Jr. (2008). "Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity." J Exp Med 205(7): 1523-7.


276. Ichinohe, T., H. K. Lee, et al. (2009). "Inflammasome recognition of influenza virus is essential for adaptive immune responses." J Exp Med 206(1): 79-87.


277. Uzri, D. and L. Gehrke (2009). "Nucleotide sequences and modifications that determine RIG-I/RNA binding and signaling activities." J Virol.


278. Aliyari, R. and S. W. Ding (2009). "RNA-based viral immunity initiated by the Dicer family of host immune receptors." Immunol Rev 227(1): 176-88.


279. Rosenberg, H. F. (2008). "RNase A ribonucleases and host defense: an evolving story." J Leukoc Biol 83(5): 1079-87.


280. Schmidt, A., T. Schwerd, et al. (2009). "5'-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I." Proc Natl Acad Sci U S A.


281. Bisbal, C. and R. H. Silverman (2007). "Diverse functions of RNase L and implications in pathology." Biochimie 89(6-7): 789-98.


282. Besch, R., H. Poeck, et al. (2009). "Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells." J Clin Invest 119(8): 2399-411.


283. Hornung, V., A. Ablasser, et al. (2009). "AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC." Nature 458(7237): 514-8.


284. Ganguly, D., G. Chamilos, et al. (2009). "Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8." J Exp Med 206(9): 1983- 94.


285. Barral, P. M., D. Sarkar, et al. (2009). "RIG-I is cleaved during picornavirus infection." Virology 391(2): 171-6.


286. Chiu, Y. H., J. B. Macmillan, et al. (2009). "RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway." Cell 138(3): 576-91.


287. Choi, M. K., Z. Wang, et al. (2009). "A selective contribution of the RIG-I-like receptor pathway to type I interferon responses activated by cytosolic DNA." Proc Natl Acad Sci U S A 106(42): 17870-5.


288. Ikegame, S., M. Takeda, et al. (2010). "Both RIG-I and MDA5 RNA helicases contribute to the induction of alpha/beta interferon in measles virus-infected human cells." J Virol 84(1): 372-9.


289. Allen, I. C., M. A. Scull, et al. (2009). "The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA." Immunity 30(4): 556-65.


290. Ishikawa, H. O. a. and G. N. Barber (2008). "STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling." Nature 455(7213): 674-8.


291. Luhtala, N. and R. Parker (2010). "T2 Family ribonucleases: ancient enzymes with diverse roles." Trends Biochem Sci.


292. Alalwani, M. S., J. Sierigk, et al. (2010). "The antimicrobial peptide LL-37 modulates the inflammatory and host defense response of human neutrophils." Eur J Immunol.


293. Lau, Y. E. O. L.-A., D. M. Bowdish, et al. (2006). "Apoptosis of airway epithelial cells: human serum sensitive induction by the cathelicidin LL-37." Am J Respir Cell Mol Biol 34(4): 399-409.


294. Bird, A. P. (1986). "CpG-rich islands and the function of DNA methylation." Nature 321(6067): 209-13.


295. Barral, P. M., D. Sarkar, et al. (2009). "Functions of the cytoplasmic RNA sensors RIG-I and MDA-5: Key regulators of innate immunity." Pharmacol Ther.


296. Akira, S. O. T., S. Uematsu, et al. (2006). "Pathogen recognition and innate immunity." Cell 124(4): 783-801.


297. Myong, S., S. Cui, et al. (2009). "Cytosolic Viral Sensor RIG-I Is a 5'-Triphosphate- Dependent Translocase on Double-Stranded RNA." Science.


298. Malathi, K., B. Dong, et al. (2007). "Small self-RNA generated by RNase L amplifies antiviral innate immunity." Nature 448(7155): 816-9.


299. Zelphati, O. O. D. and F. C. Szoka, Jr. (1996). "Mechanism of oligonucleotide release from cationic liposomes." Proc Natl Acad Sci U S A 93(21): 11493-8.


300. Lund, J. M. r. o. v. a. i., L. Alexopoulou, et al. (2004). "Recognition of single-stranded RNA viruses by Toll-like receptor 7." Proc Natl Acad Sci U S A 101(15): 5598-603.


301. Gudmundsson, G. H., K. P. Magnusson, et al. (1995). "Structure of the gene for porcine peptide antibiotic PR-39, a cathelin gene family member: comparative mapping of the locus for the human peptide antibiotic FALL-39." Proc Natl Acad Sci U S A 92(15): 7085-9.


302. O'Hagan, D. T., M. L. MacKichan, et al. (2001). "Recent developments in adjuvants for vaccines against infectious diseases." Biomol Eng 18(3): 69-85.


303. Volbeda, A., A. Lahm, et al. (1991). "Crystal structure of Penicillium citrinum P1 nuclease at 2.8 A resolution." Embo J 10(7): 1607-18.


304. Means, T. K., E. Latz, et al. (2005). "Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9." J Clin Invest 115(2): 407-17.


305. Bauer, S. O. T., C. J. Kirschning, et al. (2001). "Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition." Proc Natl Acad Sci U S A 98(16): 9237-42.


306. Zanetti, M., R. Gennaro, et al. (1995). "Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain." FEBS Lett 374(1): 1-5.


307. Klenk, H. D. I. H., R. Rott, et al. (1975). "Activation of influenza A viruses by trypsin treatment." Virology 68(2): 426-39.


308. Sorensen, O., J. B. Cowland, et al. (1997). "An ELISA for hCAP-18, the cathelicidin present in human neutrophils and plasma." J Immunol Methods 206(1-2): 53-9.


309. Haas, T. O. D., J. Metzger, et al. (2008). "The DNA sugar backbone 2' deoxyribose determines toll-like receptor 9 activation." Immunity 28(3): 315-23.


310. Takahasi, K. o. R. I., M. Yoneyama, et al. (2008). "Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses." Mol Cell 29(4): 428- 40.


311. Hornung, V. O. R.-I., J. Ellegast, et al. (2006). "5'-Triphosphate RNA is the ligand for RIG- I." Science 314(5801): 994-7.


312. Astriab-Fisher, A., M. H. Fisher, et al. (2004). "Increased uptake of antisense oligonucleotides by delivery as double stranded complexes." Biochem Pharmacol 68(3): 403-7.