Acute respiratory tract infection (RTI) is a leading cause of morbidity and mortality worldwide and the majority of RTIs are caused by viruses, among which respiratory syncytial virus (RSV) and the closely related human metapneumovirus (hMPV) figure prominently. Host innate immune response has been implicated in recognition, protection and immune pathological mechanisms. Host-viral interactions are generally initiated via host recognition of pathogen-associated molecular patterns (PAMPs) of the virus. This recognition occurs through host pattern recognition receptors (PRRs) which are expressed on innate immune cells such as epithelial cells, dendritic cells, macrophages and neutrophils. Multiple PRR families, including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs), contribute significantly to viral detection, leading to induction of cytokines, chemokines and type I interferons (IFNs), which subsequently facilitate the eradication of the virus. This review focuses on the current literature on RSV and hMPV infection and the role of PRRs in establishing/mediating the infection in both in vitro and in vivo models. A better understanding of the complex interplay between these two viruses and host PRRs might lead to efficient prophylactic and therapeutic treatments, as well as the development of adequate vaccines.
References
[1]
Papadopoulos, N.G.; Skevaki, C.L. Viruses of the Lung. In Encyclopedia of Respiratory Medicine; Geoffrey, J.L., Steven, D.S., Eds.; Academic Press: Oxford, UK, 2006; pp. 483–488.
[2]
Lamb, R.A.K.D. Paramyxoviridae: The Viruses and Their Replication. In Fundamental Virology, 4th; Knipe, D.M., Howley, P.M., Eds.; Lippincott, Williams and Wilkins: Philadelphia, PA, USA, 2001; pp. 689–724.
[3]
Blount, R.E., Jr.; Morris, J.A.; Savage, R.E. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc. Soc. Exp. Biol. Med. 1956, 92, 544–549.
[4]
Chanock, R.; Roizman, B.; Myers, R. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. Am. J. Hyg. 1957, 66, 281–290.
[5]
Chanock, R.; Finberg, L. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). II. Epidemiologic aspects of infection in infants and young children. Am. J. Hyg. 1957, 66, 291–300.
[6]
Glezen, W.P.; Taber, L.H.; Frank, A.L. Risk of primary infection and reinfection with respiratory syncytial virus. Am. J. Dis. Child. 1986, 140, 543–546.
[7]
Hall, C.B. Respiratory syncytial virus and parainfluenza virus. N. Engl. J. Med. 2001, 344, 1917–1928, doi:10.1056/NEJM200106213442507.
[8]
Mufson, M.A.; Orvell, C.; Rafnar, B.; Norrby, E. Two distinct subtypes of human respiratory syncytial virus. J. Gen. Virol. 1985, 66 (Pt. 10), 2111–2124.
Beckham, J.D.; Cadena, A.; Lin, J.; Piedra, P.A.; Glezen, W.P.; Greenberg, S.B.; Atmar, R.L. Respiratory viral infections in patients with chronic, obstructive pulmonary disease. J. Infect. 2005, 50, 322–330, doi:10.1016/j.jinf.2004.07.011.
[11]
Atreya, P.L.; Kulkarni, S. Respiratory syncytial virus strain A2 is resistant to the antiviral effects of type I interferons and human MxA. Virology 1999, 261, 227–241, doi:10.1006/viro.1999.9835.
[12]
Ferris, J.A.; Aherne, W.A.; Locke, W.S. Sudden and unexpected deaths to infants: Histology and virology. Br. Med. J. 1973, 2, 439–449, doi:10.1136/bmj.2.5864.439.
[13]
Fiedler, M.A.; Wernke-Dollries, K.; Stark, J.M. Inhibition of viral replication reverses respiratory syncytial virus-induced NF-kB activation and interleukin-8 gene expression in A549 cells. J. Virol. 1996, 70, 9079–9082.
[14]
Fiedler, M.A.; Wernke-Dollries, K. Incomplete regulation of NF-kappaB by IkappaBalpha during respiratory syncytial virus infection in A549 cells. J. Virol. 1999, 73, 4502–4507.
[15]
Garofalo, R.P.; Sabry, M.; Jamaluddin, M.; Yu, R.K.; Casola, A.; Ogra, P.L.; Brasier, A.R. Transcriptional activation of the interleukin-8 gene by respiratory syncytial virus infection in alveolar epithelial cells: Nuclear translocation of the RelA transcription factor as a mechanism producing airway mucosal inflammation. J. Virol. 1996, 70, 8773–8781.
[16]
Jamaluddin, M.; Casola, A.; Garofalo, R.P.; Han, Y.; Elliott, T.; Ogra, P.L.; Brasier, A.R. The major component of IkBa proteolysis occurs independently of the proteasome pathway in Respiratory Syncytial Virus-infected pulmonary epithelial cells. J. Virol. 1998, 72, 4849–4857.
[17]
Olszewska-Pazdrak, B.; Casola, A.; Saito, T.; Alam, R.; Crowe, S.E.; Mei, F.; Ogra, P.L.; Garofalo, R.P. Cell-Specific expression of RANTES, MCP-1, and MIP-1alpha by lower airway epithelial cells and eosinophils infected with respiratory syncytial virus. J. Virol. 1998, 72, 4756–4764.
[18]
Zhang, Y.; Luxon, B.A.; Casola, A.; Garofalo, R.P.; Jamaluddin, M.; Brasier, A.R. Expression of respiratory syncytial virus-induced chemokine gene networks in lower airway epithelial cells revealed by cDNA microarrays. J. Virol. 2001, 75, 9044–9058, doi:10.1128/JVI.75.19.9044-9058.2001.
[19]
Van den Hoogen, B.G.; de Jong, J.C.; Groen, J.; Kuiken, T.; de Groot, R.; Fouchier, R.A.; Osterhaus, A.D. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat. Med. 2001, 7, 719–724, doi:10.1038/89098.
[20]
Feuillet, F.; Lina, B.; Rosa-Calatrava, M.; Boivin, G. Ten years of human metapneumovirus research. J. Clin. Virol. 2012, 53, 97–105, doi:10.1016/j.jcv.2011.10.002.
[21]
Principi, N.; Bosis, S.; Esposito, S. Human metapneumovirus in paediatric patients. Clin. Microbiol. Infect. 2006, 12, 301–308, doi:10.1111/j.1469-0691.2005.01325.x.
[22]
Kahn, J.S. Epidemiology of human metapneumovirus. Clin. Microbiol. Rev. 2006, 19, 546–557, doi:10.1128/CMR.00014-06.
[23]
Williams, J.V.; Harris, P.A.; Tollefson, S.J.; Halburnt-Rush, L.L.; Pingsterhaus, J.M.; Edwards, K.M.; Wright, P.F.; Crowe, J.E., Jr. Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children. N. Engl. J. Med. 2004, 350, 443–450, doi:10.1056/NEJMoa025472.
[24]
Crowe, J.E., Jr. Human metapneumovirus as a major cause of human respiratory tract disease. Pediatr. Infect. Dis. J. 2004, 23, S215–S221, doi:10.1097/01.inf.0000144668.81573.6d.
[25]
Biovin, G.; Abed, L.; Pelletier, G.; Ruel, L.; Moisan, D.; Cote', S.; Peret, T.C.; Erdman, D.D.; Anderson, L.J. Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratort-tract infections in all age groups. J Infect Dis 2002, 186, 1330–1334, doi:10.1086/344319.
[26]
Esper, F.; Boucher, D.; Weibel, C.; Martinello, R.A.; Kahn, J.S. Human metapneumovirus infection in the United States: Clinical manifestations associated with a newly emerging respiratory infection in children. Pediatrics 2003, 111, 1407–1410, doi:10.1542/peds.111.6.1407.
[27]
Guerrero-Plata, A.; Casola, A.; Garofalo, R.P. Human metapneumovirus induces a profile of lung cytokines distinct from that of respiratory syncytial virus. J. Virol. 2005, 79, 14992–14997, doi:10.1128/JVI.79.23.14992-14997.2005.
[28]
Guerrero-Plata, A.; Casola, A.; Suarez, G.; Yu, X.; Spetch, L.; Peeples, M.E.; Garofalo, R.P. Differential response of dendritic cells to human metapneumovirus and respiratory syncytial virus. Am. J. Respir. Cell Mol. Biol. 2006, 34, 320–329.
[29]
Bao, X.; Liu, T.; Spetch, L.; Kolli, D.; Garofalo, R.P.; Casola, A. Airway epithelial cell response to human metapneumovirus infection. Virology 2007, 368, 91–101, doi:10.1016/j.virol.2007.06.023.
[30]
Kumar, H.; Kawai, T.; Akira, S. Toll-Like receptors and innate immunity. Biochem. Biophys. Res. Commun. 2009, 388, 621–625, doi:10.1016/j.bbrc.2009.08.062.
Sabbah, A.; Chang, T.H.; Harnack, R.; Frohlich, V.; Tominaga, K.; Dube, P.H.; Xiang, Y.; Bose, S. Activation of innate immune antiviral responses by Nod2. Nat. Immunol. 2009, 10, 1073–1080, doi:10.1038/ni.1782.
[33]
Loo, Y.M.; Fornek, J.; Crochet, N.; Bajwa, G.; Perwitasari, O.; Martinez-Sobrido, L.; Akira, S.; Gill, M.A.; Garcia-Sastre, A.; Katze, M.G.; et al. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J. Virol. 2008, 82, 335–345, doi:10.1128/JVI.01080-07.
[34]
Kawai, T.; Akira, S. Antiviral signaling through pattern recognition receptors. J. Biochem. (Tokyo) 2006, 141, 137–145.
[35]
Leulier, F.; Lemaitre, B. Toll-like receptors--taking an evolutionary approach. Nat. Rev. Genet. 2008, 9, 165–178, doi:10.1038/nrg2303.
[36]
Kawai, T.; Akira, S. The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors. Nat. Immunol. 2010, 11, 373–384, doi:10.1038/ni.1863.
[37]
Koblansky, A.A.; Jankovic, D.; Oh, H.; Hieny, S.; Sungnak, W.; Mathur, R.; Hayden, M.S.; Akira, S.; Sher, A.; Ghosh, S. Recognition of profilin by toll-like receptor 12 Is critical for host resistance to toxoplasma gondii. Immunity 2013, 38, 119–130, doi:10.1016/j.immuni.2012.09.016.
[38]
Oldenburg, M.; Kruger, A.; Ferstl, R.; Kaufmann, A.; Nees, G.; Sigmund, A.; Bathke, B.; Lauterbach, H.; Suter, M.; Dreher, S.; et al. TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification. Science 2012, 337, 1111–1115, doi:10.1126/science.1220363.
[39]
He, X.; Jia, H.; Jing, Z.; Liu, D. Recognition of pathogen-associated nucleic acids by endosomal nucleic acid-sensing toll-like receptors. Acta Biochim. Biophys. Sin. 2013, 45, 241–258, doi:10.1093/abbs/gms122.
Takeda, K.; Akira, S. Toll-Like receptors in innate immunity. Int. Immunol. 2005, 17, 1–14, doi:10.1093/intimm/dxh186.
[42]
Chen, Z.J. Ubiquitin signalling in the NF-kappaB pathway. Nat. Cell Biol. 2005, 7, 758–765, doi:10.1038/ncb0805-758.
[43]
Sato, S.; Sanjo, H.; Takeda, K.; Ninomiya-Tsuji, J.; Yamamoto, M.; Kawai, T.; Matsumoto, K.; Takeuchi, O.; Akira, S. Essential function for the kinase TAK1 in innate and adaptive immune responses. Nat. Immunol. 2005, 6, 1087–1095, doi:10.1038/ni1255.
[44]
Funami, K.; Matsumoto, M.; Oshiumi, H.; Akazawa, T.; Yamamoto, A.; Seya, T. The cytoplasmic 'linker region' in Toll-like receptor 3 controls receptor localization and signaling. Int. Immunol. 2004, 16, 1143–1154, doi:10.1093/intimm/dxh115.
[45]
Yamamoto, M.; Sato, S.; Hemmi, H.; Hoshino, K.; Kaisho, T.; Sanjo, H.; Takeuchi, O.; Sugiyama, M.; Okabe, M.; Takeda, K.; et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 2003, 301, 640–643, doi:10.1126/science.1087262.
[46]
Meylan, E.; Burns, K.; Hofmann, K.; Blancheteau, V.; Martinon, F.; Kelliher, M.; Tschopp, J. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat. Immunol. 2004, 5, 503–507, doi:10.1038/ni1061.
[47]
Mayer, A.K.; Muehmer, M.; Mages, J.; Gueinzius, K.; Hess, C.; Heeg, K.; Bals, R.; Lang, R.; Dalpke, A.H. Differential recognition of TLR-dependent microbial ligands in human bronchial epithelial cells. J. Immunol. 2007, 178, 3134–3142.
[48]
Muir, A.; Soong, G.; Sokol, S.; Reddy, B.; Gomez, M.I.; Van, H.A.; Prince, A. Toll-Like receptors in normal and cystic fibrosis airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 2004, 30, 777–783.
[49]
Ioannidis, I.; Ye, F.; McNally, B.; Willette, M.; Flano, E. TLR expression and induction of type I and type III interferons in primary airway epithelial cells. J. Virol 2013, 87, 3261–3270, doi:10.1128/JVI.01956-12.
[50]
Maris, N.A.; Dessing, M.C.; de Vos, A.F.; Bresser, P.; van der Zee, J.S.; Jansen, H.M.; Spek, C.A.; van der Poll, T. Toll-Like receptor mRNA levels in alveolar macrophages after inhalation of endotoxin. Eur. Respir. J. 2006, 28, 622–626, doi:10.1183/09031936.06.00010806.
[51]
Oshikawa, K.; Sugiyama, Y. Gene expression of Toll-like receptors and associated molecules induced by inflammatory stimuli in the primary alveolar macrophage. Biochem. Biophys. Res. Commun. 2003, 305, 649–655, doi:10.1016/S0006-291X(03)00837-4.
[52]
Suzuki, K.; Suda, T.; Naito, T.; Ide, K.; Chida, K.; Nakamura, H. Impaired toll-like receptor 9 expression in alveolar macrophages with no sensitivity to CpG DNA. Am. J. Respir. Crit. Care Med. 2005, 171, 707–713, doi:10.1164/rccm.200408-1078OC.
[53]
Demedts, I.K.; Brusselle, G.G.; Vermaelen, K.Y.; Pauwels, R.A. Identification and characterization of human pulmonary dendritic cells. Am. J. Respir. Cell Mol. Biol. 2005, 32, 177–184, doi:10.1165/rcmb.2004-0279OC.
[54]
Holt, P.G.; Strickland, D.H.; Wikstrom, M.E.; Jahnsen, F.L. Regulation of immunological homeostasis in the respiratory tract. Nat. Rev. Immunol. 2008, 8, 142–152, doi:10.1038/nri2236.
[55]
Masten, B.J.; Olson, G.K.; Tarleton, C.A.; Rund, C.; Schuyler, M.; Mehran, R.; Archibeque, T.; Lipscomb, M.F. Characterization of myeloid and plasmacytoid dendritic cells in human lung. J. Immunol. 2006, 177, 7784–7793.
[56]
Fan, J.; Frey, R.S.; Malik, A.B. TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase. J. Clin. Invest. 2003, 112, 1234–1243.
Opitz, B.; van, L.V.; Eitel, J.; Suttorp, N. Innate immune recognition in infectious and noninfectious diseases of the lung. Am. J. Respir. Crit. Care Med. 2010, 181, 1294–1309, doi:10.1164/rccm.200909-1427SO.
Kolli, D.; Bao, X.; Liu, T.; Hong, C.; Wang, T.; Garofalo, R.P.; Casola, A. Human metapneumovirus glycoprotein G inhibits TLR4-dependent signaling in monocyte-derived dendritic cells. J. Immunol. 2011, 187, 47–54, doi:10.4049/jimmunol.1002589.
[66]
Goutagny, N.; Jiang, Z.; Tian, J.; Parroche, P.; Schickli, J.; Monks, B.G.; Ulbrandt, N.; Ji, H.; Kiener, P.A.; Coyle, A.J.; et al. Cell type-specific recognition of human metapneumoviruses (HMPVs) by retinoic acid-inducible gene I (RIG-I) and TLR7 and viral interference of RIG-I ligand recognition by HMPV-B1 phosphoprotein. J. Immunol. 2010, 184, 1168–1179, doi:10.4049/jimmunol.0902750.
[67]
Imran, M.; Waheed, Y.; Manzoor, S.; Bilal, M.; Ashraf, W.; Ali, M.; Ashraf, M. Interaction of Hepatitis C virus proteins with pattern recognition receptors. Virol. J. 2012, 9, 126, doi:10.1186/1743-422X-9-126.
[68]
Villalba, M.; Hott, M.; Martin, C.; Aguila, B.; Valdivia, S.; Quezada, C.; Zambrano, A.; Concha, M.I.; Otth, C. Herpes simplex virus type 1 induces simultaneous activation of Toll-like receptors 2 and 4 and expression of the endogenous ligand serum amyloid A in astrocytes. Med. Microbiol. Immunol. 2012, 201, 371–379, doi:10.1007/s00430-012-0247-0.
[69]
Zhou, S.; Halle, A.; Kurt-Jones, E.A.; Cerny, A.M.; Porpiglia, E.; Rogers, M.; Golenbock, D.T.; Finberg, R.W. Lymphocytic choriomeningitis virus (LCMV) infection of CNS glial cells results in TLR2-MyD88/Mal-dependent inflammatory responses. J. Neuroimmunol. 2008, 194, 70–82, doi:10.1016/j.jneuroim.2007.11.018.
[70]
Chaudhuri, S.; Lowen, B.; Chan, G.; Davey, A.; Riddell, M.; Guilbert, L.J. Human cytomegalovirus interacts with toll-like receptor 2 and CD14 on syncytiotrophoblasts to stimulate expression of TNFalpha mRNA and apoptosis. Placenta 2009, 30, 994–1001, doi:10.1016/j.placenta.2009.09.001.
[71]
Cyr, S.L.; Jones, T.; Stoica-Popescu, I.; Burt, D.; Ward, B.J. C57Bl/6 mice are protected from respiratory syncytial virus (RSV) challenge and IL-5 associated pulmonary eosinophilic infiltrates following intranasal immunization with Protollin-eRSV vaccine. Vaccine 2007, 25, 3228–3232, doi:10.1016/j.vaccine.2007.01.037.
[72]
Hancock, G.E.; Heers, K.M.; Pryharski, K.S.; Smith, J.D.; Tiberio, L. Adjuvants recognized by toll-like receptors inhibit the induction of polarized type 2 T cell responses by natural attachment (G) protein of respiratory syncytial virus. Vaccine 2003, 21, 4348–4358, doi:10.1016/S0264-410X(03)00482-1.
[73]
Janssen, R.; Pennings, J.; Hodemaekers, H.; Buisman, A.; van Oosten, M.; de Rond, L.; Ozturk, K.; Dormans, J.; Kimman, T.; Hoebee, B. Host transcription profiles upon primary respiratory syncytial virus infection. J. Virol. 2007, 81, 5958–5967, doi:10.1128/JVI.02220-06.
Mailaparambil, B.; Krueger, M.; Heinze, J.; Forster, J.; Heinzmann, A. Polymorphisms of toll like receptors in the genetics of severe RSV associated diseases. Dis. Markers 2008, 25, 59–65.
[76]
Daley, D.; Park, J.E.; He, J.Q.; Yan, J.; Akhabir, L.; Stefanowicz, D.; Becker, A.B.; Chan-Yeung, M.; Bosse, Y.; Kozyrskyj, A.L.; et al. Associations and interactions of genetic polymorphisms in innate immunity genes with early viral infections and susceptibility to asthma and asthma-related phenotypes. J. Allergy Clin. Immunol. 2012, 130, 1284–1293, doi:10.1016/j.jaci.2012.07.051.
[77]
Kukavica-Ibrulj, I.; Hamelin, M.E.; Prince, G.A.; Gagnon, C.; Bergeron, Y.; Bergeron, M.G.; Boivin, G. Infection with human metapneumovirus predisposes mice to severe pneumococcal pneumonia. J. Virol. 2009, 83, 1341–1349, doi:10.1128/JVI.01123-08.
[78]
Matsumoto, M.; Funami, K.; Tanabe, M.; Oshiumi, H.; Shingai, M.; Seto, Y.; Yamamoto, A.; Seya, T. Subcellular localization of Toll-like receptor 3 in human dendritic cells. J. Immunol. 2003, 171, 3154–3162.
[79]
Rudd, B.D.; Burstein, E.; Duckett, C.S.; Li, X.; Lukacs, N.W. Differential role for TLR3 in respiratory syncytial virus-induced chemokine expression. J. Virol. 2005, 79, 3350–3357, doi:10.1128/JVI.79.6.3350-3357.2005.
[80]
Groskreutz, D.J.; Monick, M.M.; Powers, L.S.; Yarovinsky, T.O.; Look, D.C.; Hunninghake, G.W. Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells. J. Immunol. 2006, 176, 1733–1740.
[81]
Liu, P.; Jamaluddin, M.; Li, K.; Garofalo, R.P.; Casola, A.; Brasier, A.R. Retinoic Acid-inducible gene I mediates early antiviral response and toll-like receptor 3 expression in respiratory syncytial virus-infected airway epithelial cells. J. Virol. 2007, 81, 1401–1411, doi:10.1128/JVI.01740-06.
[82]
Lukacs, N.W.; Tekkanat, K.K.; Berlin, A.; Hogaboam, C.M.; Miller, A.; Evanoff, H.; Lincoln, P.; Maassab, H. Respiratory syncytial virus predisposes mice to augmented allergic airway responses via IL-13-mediated mechanisms. J. Immunol. 2001, 167, 1060–1065.
Huang, S.; Wei, W.; Yun, Y. Upregulation of TLR7 and TLR3 gene expression in the lung of respiratory syncytial virus infected mice. Wei Sheng Wu Xue Bao 2009, 49, 239–245.
[85]
Boukhvalova, M.S.; Sotomayor, T.B.; Point, R.C.; Pletneva, L.M.; Prince, G.A.; Blanco, J.C. Activation of interferon response through toll-like receptor 3 impacts viral pathogenesis and pulmonary toll-like receptor expression during respiratory syncytial virus and influenza infections in the cotton rat Sigmodon hispidus model. J. Interf. Cytokine Res. 2010, 30, 229–242.
Aeffner, F.; Traylor, Z.P.; Yu, E.N.; Davis, I.C. Double-Stranded RNA induces similar pulmonary dysfunction to respiratory syncytial virus in BALB/c mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 2011, 301, L99–L109, doi:10.1152/ajplung.00398.2010.
[88]
Guerrero-Plata, A.; Baron, S.; Poast, J.S.; Adegboyega, P.A.; Casola, A.; Garofalo, R.P. Activity and regulation of alpha interferon in respiratory syncytial virus and human metapneumovirus experimental infections. J. Virol. 2005, 79, 10190–10199.
[89]
Scagnolari, C.; Midulla, F.; Pierangeli, A.; Moretti, C.; Bonci, E.; Berardi, R.; De, A.D.; Selvaggi, C.; Di, M.P.; Girardi, E.; et al. Gene expression of nucleic acid-sensing pattern recognition receptors in children hospitalized for respiratory syncytial virus-associated acute bronchiolitis. Clin. Vaccine Immunol. 2009, 16, 816–823, doi:10.1128/CVI.00445-08.
[90]
Dou, Y.; Zhao, Y.; Zhang, Z.Y.; Zhao, X.D. Toll-Like receptors expression in the lungs of human metapneumovirus infected mice and the effects of polyI:C on viral infection. Bing Du Xue Bao 2010, 26, 1–7.
[91]
Finberg, R.W.; Wang, J.P.; Kurt-Jones, E.A. Toll like receptors and viruses. Rev. Med. Virol. 2007, 17, 35–43, doi:10.1002/rmv.525.
[92]
O'Mahony, D.S.; Pham, U.; Iyer, R.; Hawn, T.R.; Liles, W.C. Differential constitutive and cytokine-modulated expression of human Toll-like receptors in primary neutrophils, monocytes, and macrophages. Int. J. Med. Sci. 2008, 5, 1–8.
[93]
Sabroe, I.; Jones, E.C.; Usher, L.R.; Whyte, M.K.; Dower, S.K. Toll-Like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a critical role for monocytes in leukocyte lipopolysaccharide responses. J. Immunol. 2002, 168, 4701–4710.
[94]
Shimazu, R.; Akashi, S.; Ogata, H.; Nagai, Y.; Fukudome, K.; Miyake, K.; Kimoto, M. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 1999, 189, 1777–1782, doi:10.1084/jem.189.11.1777.
[95]
Viriyakosol, S.; Kirkland, T.; Soldau, K.; Tobias, P. MD-2 binds to bacterial lipopolysaccharide. J. Endotoxin. Res. 2000, 6, 489–491.
[96]
Kim, H.M.; Park, B.S.; Kim, J.I.; Kim, S.E.; Lee, J.; Oh, S.C.; Enkhbayar, P.; Matsushima, N.; Lee, H.; Yoo, O.J.; et al. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 2007, 130, 906–917, doi:10.1016/j.cell.2007.08.002.
[97]
Da Costa, C.U.; Wantia, N.; Kirschning, C.J.; Busch, D.H.; Rodriguez, N.; Wagner, H.; Miethke, T. Heat shock protein 60 from Chlamydia pneumoniae elicits an unusual set of inflammatory responses via Toll-like receptor 2 and 4 in vivo. Eur. J. Immunol. 2004, 34, 2874–2884.
[98]
Dogan, S.; Zhang, Q.; Pridmore, A.C.; Mitchell, T.J.; Finn, A.; Murdoch, C. Pneumolysin-induced CXCL8 production by nasopharyngeal epithelial cells is dependent on calcium flux and MAPK activation via Toll-like receptor 4. Microbes. Infect. 2011, 13, 65–75, doi:10.1016/j.micinf.2010.10.003.
[99]
Okumura, A.; Pitha, P.M.; Yoshimura, A.; Harty, R.N. Interaction between Ebola virus glycoprotein and host toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1. J. Virol. 2010, 84, 27–33, doi:10.1128/JVI.01462-09.
[100]
Barrera, V.; Skorokhod, O.A.; Baci, D.; Gremo, G.; Arese, P.; Schwarzer, E. Host fibrinogen stably bound to hemozoin rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin: A new paradigm of hemozoin action. Blood 2011, 117, 5674–5682, doi:10.1182/blood-2010-10-312413.
Rallabhandi, P.; Phillips, R.L.; Boukhvalova, M.S.; Pletneva, L.M.; Shirey, K.A.; Gioannini, T.L.; Weiss, J.P.; Chow, J.C.; Hawkins, L.D.; Vogel, S.N.; Blanco, J.C.G. Respiratory syncytial virus fusion protein-induced Toll-Like Receptor 4 (TLR4) signaling is inhibited by the TLR4 antagonists rhodobacter sphaeroides lipopolysaccharide and Eritoran (E5564) and requires direct interaction with MD-2. mBio 2012, 3, 218–212.
[108]
Lizundia, R.; Sauter, K.S.; Taylor, G.; Werling, D. Host species-specific usage of the TLR4-LPS receptor complex. Innate Immun. 2008, 14, 223–231, doi:10.1177/1753425908095957.
[109]
Marr, N.; Turvey, S.E. Role of human TLR4 in respiratory syncytial virus-induced NF-kappaB activation, viral entry and replication. Innate Immun. 2012, 18, 856–865, doi:10.1177/1753425912444479.
Xie, X.H.; Law, H.K.; Wang, L.J.; Li, X.; Yang, X.Q.; Liu, E.M. Lipopolysaccharide induces IL-6 production in respiratory syncytial virus-infected airway epithelial cells through the toll-like receptor 4 signaling pathway. Pediatr. Res. 2009, 65, 156–162, doi:10.1203/PDR.0b013e318191f5c6.
[112]
Xie, X.H.; Liu, E.M.; Yang, X.Q.; Law, H.K.; Li, X.; Wang, L.J.; Liu, W.; Xu, W.F. Toll-Like receptor 4 expression and function of respiratory syncytial virus-infected airway epithelial cells. Zhonghua Jie He He Hu Xi Za Zhi 2008, 31, 213–217.
[113]
Marchant, D.; Singhera, G.K.; Utokaparch, S.; Hackett, T.L.; Boyd, J.H.; Luo, Z.; Si, X.; Dorscheid, D.R.; McManus, B.M.; Hegele, R.G. Toll-Like receptor 4-mediated activation of p38 mitogen-activated protein kinase is a determinant of respiratory virus entry and tropism. J. Virol. 2010, 84, 11359–11373, doi:10.1128/JVI.00804-10.
[114]
Haynes, L.M.; Moore, D.D.; Kurt-Jones, E.A.; Finberg, R.W.; Anderson, L.J.; Tripp, R.A. Involvement of toll-like receptor 4 in innate immunity to respiratory syncytial virus. J. Virol. 2001, 75, 10730–10737.
[115]
Ehl, S.; Bischoff, R.; Ostler, T.; Vallbracht, S.; Schulte-Monting, J.; Poltorak, A.; Freudenberg, M. The role of Toll-like receptor 4 versus interleukin-12 in immunity to respiratory syncytial virus. Eur. J. Immunol. 2004, 34, 1146–1153, doi:10.1002/eji.200324449.
[116]
Haeberle, H.; Takizawa, R.; Casola, A.; Brasier, A.R.; Dieterich, H.-J.; van Rooijen, N.; Gatalica, Z.; Garofalo, R.P. Respiratory syncytial virus-induced activation of NF-kB in the lung involves alveolar macrophages and Toll-like receptor 4-dependent pathways. J. Infect. Dis. 2002, 186, 1199–1206, doi:10.1086/344644.
[117]
Shirey, K.A.; Pletneva, L.M.; Puche, A.C.; Keegan, A.D.; Prince, G.A.; Blanco, J.C.; Vogel, S.N. Control of RSV-induced lung injury by alternatively activated macrophages is IL-4R alpha-, TLR4-, and IFN-beta-dependent. Mucosal Immunol. 2010, 3, 291–300.
[118]
Kunzelmann, K.; Sun, J.; Meanger, J.; King, N.J.; Cook, D.I. Inhibition of airway Na+ transport by respiratory syncytial virus. J. Virol. 2007, 81, 3714–3720, doi:10.1128/JVI.02621-06.
[119]
Cyr, S.L.; Angers, I.; Guillot, L.; Stoica-Popescu, I.; Lussier, M.; Qureshi, S.; Burt, D.S.; Ward, B.J. TLR4 and MyD88 control protection and pulmonary granulocytic recruitment in a murine intranasal RSV immunization and challenge model. Vaccine 2009, 27, 421–430, doi:10.1016/j.vaccine.2008.10.073.
[120]
Boukhvalova, M.S.; Prince, G.A.; Soroush, L.; Harrigan, D.C.; Vogel, S.N.; Blanco, J.C.G. The TLR4 agonist, monophosphoryl lipid A, attenuates the cytokine storm associated with respiratory syncytial virus vaccine-enhanced disease. Vaccine 2006, 24, 5027–5035, doi:10.1016/j.vaccine.2006.03.064.
[121]
Numata, M.; Chu, H.W.; Dakhama, A.; Voelker, D.R. Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virusG？？induced inflammation and infection. Proc. Natl. Acad. Sci. USA 2010, 107, 320–325, doi:10.1073/pnas.0909361107.
[122]
Gagro, A.; Tominac, M.; Krsulovic-Hresic, V.; Bace, A.; Matic, M.; Drazenovic, V.; Mlinaric- Galinovic, G.; Kosor, E.; Gotovac, K.; Bolanca, I.; et al. Increased Toll-like receptor 4 expression in infants with respiratory syncytial virus bronchiolitis. Clin. Exp. Immunol. 2004, 135, 267–272, doi:10.1111/j.1365-2249.2004.02364.x.
[123]
Halfhide, C.P.; Brearey, S.P.; Flanagan, B.F.; Hunt, J.A.; Howarth, D.; Cummerson, J.; Edwards, S.; Hart, C.A.; Smyth, R.L. Neutrophil TLR4 expression is reduced in the airways of infants with severe bronchiolitis. Thorax 2009, 64, 798–805, doi:10.1136/thx.2008.107821.
[124]
Arbour, N.C.; Lorenz, E.; Schutte, B.C.; Zabner, J.; Kline, J.N.; Jones, M.; Frees, K.; Watt, J.L.; Schwartz, D.A. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat. Genet. 2000, 25, 187–191.
[125]
Miyairi, I.; Devincenzo, J.P. Human genetic factors and respiratory syncytial virus disease severity. Clin. Microbiol. Rev. 2008, 21, 686–703, doi:10.1128/CMR.00017-08.
[126]
Tal, G.; Mandelberg, A.; Dalal, I.; Cesar, K.; Somekh, E.; Tal, A.; Oron, A.; Itskovich, S.; Ballin, A.; Houri, S.; et al. Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease. J. Infect. Dis. 2004, 189, 2057–2063, doi:10.1086/420830.
[127]
Puthothu, B.; Forster, J.; Heinzmann, A.; Krueger, M. TLR-4 and CD14 polymorphisms in respiratory syncytial virus associated disease. Dis. Markers 2006, 22, 303–308.
[128]
Awomoyi, A.A.; Rallabhandi, P.; Pollin, T.I.; Lorenz, E.; Sztein, M.B.; Boukhvalova, M.S.; Hemming, V.G.; Blanco, J.C.; Vogel, S.N. Association of TLR4 polymorphisms with symptomatic respiratory syncytial virus infection in high-risk infants and young children. J. Immunol. 2007, 179, 3171–3177.
[129]
Mandelberg, A.; Tal, G.; Naugolny, L.; Cesar, K.; Oron, A.; Houri, S.; Gilad, E.; Somekh, E. Lipopolysaccharide hyporesponsiveness as a risk factor for intensive care unit hospitalization in infants with respiratory syncitial virus bronchiolitis. Clin. Exp. Immunol. 2006, 144, 48–52, doi:10.1111/j.1365-2249.2006.03030.x.
[130]
Lofgren, J.; Marttila, R.; Renko, M.; Ramet, M.; Hallman, M. Toll-Like receptor 4 Asp299Gly polymorphism in respiratory syncytial virus epidemics. Pediatr. Pulmonol. 2010, 45, 687–692, doi:10.1002/ppul.21248.
[131]
Lavoie, P.M.; Ladd, M.; Hirschfeld, A.F.; Huusko, J.; Mahlman, M.; Speert, D.P.; Hallman, M.; Lacaze-Masmonteil, T.; Turvey, S.E. Influence of common non-synonymous Toll-like receptor 4 polymorphisms on bronchopulmonary dysplasia and prematurity in human infants. PLoS One 2012, 7, e31351, doi:10.1371/journal.pone.0031351.
[132]
Kresfelder, T.L.; Janssen, R.; Bont, L.; Venter, M. Confirmation of an association between single nucleotide polymorphisms in the VDR gene with respiratory syncytial virus related disease in South African children. J. Med. Virol. 2011, 83, 1834–1840, doi:10.1002/jmv.22179.
[133]
Douville, R.N.; Lissitsyn, Y.; Hirschfeld, A.F.; Becker, A.B.; Kozyrskyj, A.L.; Liem, J.; Bastien, N.; Li, Y.; Victor, R.E.; Sekhon, M.; et al. TLR4 Asp299Gly and Thr399Ile polymorphisms: No impact on human immune responsiveness to LPS or respiratory syncytial virus. PLoS One 2010, 5, e12087, doi:10.1371/journal.pone.0012087.
[134]
Velayutham, T.S.; Kolli, D.; Ivanciuc, T.; Chao, H; Garofal, R.P.; Casola, A. Critical role of TLR4 in human metapneumovirus mediated innate immune responses and disease pathogenesisSubmitted to Plos One. .
[135]
McCartney, S.A.; Colonna, M. Viral sensors: diversity in pathogen recognition. Immunol. Rev. 2009, 227, 87–94, doi:10.1111/j.1600-065X.2008.00726.x.
[136]
Lindemans, C.A.; Coffer, P.J.; Schellens, I.M.M.; de Graaff, P.M.A.; Kimpen, J.L.L.; Koenderman, L. Respiratory Syncytial Virus Inhibits Granulocyte Apoptosis through a Phosphatidylinositol 3-Kinase and NF-κB-Dependent Mechanism. J. Immunol. 2006, 176, 5529–5537.
[137]
Phipps, S.; Lam, C.E.; Mahalingam, S.; Newhouse, M.; Ramirez, R.; Rosenberg, H.F.; Foster, P.S.; Matthaei, K.I. Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood 2007, 110, 1578–1586, doi:10.1182/blood-2007-01-071340.
[138]
McGill, J.L.; Nonnecke, B.J.; Lippolis, J.D.; Reinhardt, T.A.; Sacco, R.E. Differential chemokine and cytokine production by neonatal bovine gammadelta T cell subsets in response to viral toll-like receptor agonists and in vivo RSV infection. Immunology 2013, doi:10.1111/imm.12075.
[139]
Bendelja, K.; Vojvoda, V.; Aberle, N.; Cepin-Bogovic, J.; Gagro, A.; Mlinaric-Galinovic, G.; Rabatic, S. Decreased Toll-like receptor 8 expression and lower TNF-alpha synthesis in infants with acute RSV infection. Respir. Res. 2010, 11, 143, doi:10.1186/1465-9921-11-143.
[140]
Johnson, T.R.; Rao, S.; Seder, R.A.; Chen, M.; Graham, B.S. TLR9 agonist, but not TLR7/8, functions as an adjuvant to diminish FI-RSV vaccine-enhanced disease, while either agonist used as therapy during primary RSV infection increases disease severity. Vaccine 2009, 27, 3045–3052, doi:10.1016/j.vaccine.2009.03.026.
Becker, Y. Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy-a review. Virus Genes 2006, 33, 235–252.
[143]
Yamaguchi, Y.; Harker, J.A.; Wang, B.; Openshaw, P.J.; Tregoning, J.S.; Culley, F.J. Preexposure to CpG Protects against the Delayed Effects of Neonatal Respiratory Syncytial Virus Infection. J. Virol. 2012, 86, 10456–10461.
[144]
Yu, M.; Tong, J.H.; Mao, M.; Kan, L.X.; Liu, M.M.; Sun, Y.W.; Fu, G.; Jing, Y.K.; Yu, L.; Lepaslier, D.; et al. Cloning of a gene (RIG-G) associated with retinoic acid-induced differentiation of acute promyelocytic leukemia cells and representing a new member of a family of interferon-stimulated genes. Proc. Natl. Acad. Sci. USA 1997, 94, 7406–7411, doi:10.1073/pnas.94.14.7406.
[145]
Kang, D.C.; Gopalkrishnan, R.V.; Wu, Q.; Jankowsky, E.; Pyle, A.M.; Fisher, P.B. mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc. Natl. Acad. Sci. USA 2002, 99, 637–642.
[146]
Cui, Y.; Li, M.; Walton, K.D.; Sun, K.; Hanover, J.A.; Furth, P.A.; Hennighausen, L. The Stat3/5 locus encodes novel endoplasmic reticulum and helicase-like proteins that are preferentially expressed in normal and neoplastic mammary tissue. Genomics 2001, 78, 129–134.
[147]
Saito, T.; Hirai, R.; Loo, Y.M.; Owen, D.; Johnson, C.L.; Sinha, S.C.; 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, 582–587, doi:10.1073/pnas.0606699104.
[148]
Yoneyama, M.; Kikuchi, M.; Matsumoto, K.; Imaizumi, T.; Miyagishi, M.; Taira, K.; Foy, E.; Loo, Y.M.; Gale, M., Jr.; Akira, S.; et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J. Immunol. 2005, 175, 2851–2858.
[149]
Yoneyama, M.; Fujita, T. Function of RIG-I-like receptors in antiviral innate immunity. J. Biol. Chem. 2007, 282, 15315–15318, doi:10.1074/jbc.R700007200.
[150]
Rothenfusser, S.; Goutagny, N.; DiPerna, G.; Gong, M.; Monks, B.G.; Schoenemeyer, A.; Yamamoto, M.; Akira, S.; Fitzgerald, K.A. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J. Immunol. 2005, 175, 5260–5268.
[151]
Kawai, T.; Takahashi, K.; Sato, S.; Coban, C.; Kumar, H.; Kato, H.; Ishii, K.J.; Takeuchi, O.; Akira, S. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat. Immunol. 2005, 6, 981–988, doi:10.1038/ni1243.
[152]
Seth, R.B.; Sun, L.; Ea, C.K.; Chen, Z.J. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 2005, 122, 669–682, doi:10.1016/j.cell.2005.08.012.
[153]
Xu, L.G.; Wang, Y.Y.; Han, K.J.; Li, L.Y.; Zhai, Z.; Shu, H.B. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol. Cell 2005, 19, 727–740, doi:10.1016/j.molcel.2005.08.014.
[154]
Meylan, E.; Curran, J.; Hofmann, K.; Moradpour, D.; Binder, M.; Bartenschlager, R.; Tschopp, J. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 2005, 437, 1167–1172, doi:10.1038/nature04193.
[155]
Baril, M.; Racine, M.E.; Penin, F.; Lamarre, D. MAVS dimer is a crucial signaling component of innate immunity and the target of hepatitis C virus NS3/4A protease. J. Virol. 2009, 83, 1299–1311, doi:10.1128/JVI.01659-08.
Johnson, C.L.; Gale, M., Jr. CARD games between virus and host get a new player. Trends Immunol. 2006, 27, 1–4, doi:10.1016/j.it.2005.11.004.
[158]
Maniatis, T.; Falvo, J.V.; Kim, T.H.; Kim, T.K.; Lin, C.H.; Parekh, B.S.; Wathelet, M.G. Structure and function of the interferon-beta enhanceosome. Cold Spring Harb. Symp. Quant. Biol. 1998, 63, 609–620, doi:10.1101/sqb.1998.63.609.
[159]
Hiscott, J. Triggering the innate antiviral response through IRF-3 activation. J. Biol. Chem. 2007, 282, 15325–15329, doi:10.1074/jbc.R700002200.
[160]
Kato, H.; Sato, S.; Yoneyama, M.; Yamamoto, M.; Uematsu, S.; Matsui, K.; Tsujimura, T.; Takeda, K.; Fujita, T.; Takeuchi, O.; et al. Cell type-specific involvement of RIG-I in antiviral response. Immunity. 2005, 23, 19–28, doi:10.1016/j.immuni.2005.04.010.
[161]
Kato, H.; Takeuchi, O.; Sato, S.; Yoneyama, M.; Yamamoto, M.; Matsui, K.; Uematsu, S.; Jung, A.; Kawai, T.; Ishii, K.J.; et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006, 441, 101–105.
[162]
Liao, S.; Bao, X.; Liu, T.; Lai, S.; Li, K.; Garofalo, R.P.; Casola, A. Role of retinoic acid inducible gene-I in human metapneumovirus-induced cellular signalling. J. Gen. Virol. 2008, 89, 1978–1986, doi:10.1099/vir.0.2008/000778-0.
[163]
Gitlin, L.; Barchet, W.; Gilfillan, S.; Cella, M.; Beutler, B.; Flavell, R.A.; Diamond, M.S.; Colonna, M. Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc. Natl. Acad. Sci. USA 2006, 103, 8459–8464, doi:10.1073/pnas.0603082103.
[164]
Sasai, M.; Shingai, M.; Funami, K.; Yoneyama, M.; Fujita, T.; Matsumoto, M.; Seya, T. NAK-associated protein 1 participates in both the TLR3 and the cytoplasmic pathways in type I IFN induction. J. Immunol. 2006, 177, 8676–8683.
[165]
Liu, P.; Li, K.; Garofalo, R.P.; Brasier, A.R. Respiratory syncytial virus induces RelA release from cytoplasmic 100-kDa NF-kappa B2 complexes via a novel retinoic acid-inducible gene-I{middle dot}NF- kappa B-inducing kinase signaling pathway. J. Biol. Chem. 2008, 283, 23169–23178, doi:10.1074/jbc.M802729200.
[166]
Bhoj, V.G.; Sun, Q.; Bhoj, E.J.; Somers, C.; Chen, X.; Torres, J.P.; Mejias, A.; Gomez, A.M.; Jafri, H.; Ramilo, O.; et al. MAVS and MyD88 are essential for innate immunity but not cytotoxic T lymphocyte response against respiratory syncytial virus. Proc. Natl. Acad. Sci. USA 2008, 105, 14046–14051, doi:10.1073/pnas.0804717105.
[167]
Demoor, T.; Petersen, B.C.; Morris, S.; Mukherjee, S.; Ptaschinski, C.; De Almeida Nagata, D.E.; Kawai, T.; Ito, T.; Akira, S.; Kunkel, S.L.; et al. IPS-1 Signaling Has a Nonredundant Role in Mediating Antiviral Responses and the Clearance of Respiratory Syncytial Virus. J. Immunol. 2012, 189, 5942–5953, doi:10.4049/jimmunol.1201763.
[168]
Okabayashi, T.; Kojima, T.; Masaki, T.; Yokota, S.i.; Imaizumi, T.; Tsutsumi, H.; Himi, T.; Fujii, N.; Sawada, N. Type-III interferon, not type-I, is the predominant interferon induced by respiratory viruses in nasal epithelial cells. Virus Res. 2011, 160, 360–366, doi:10.1016/j.virusres.2011.07.011.
[169]
Vissers, M.; Remijn, T.; Oosting, M.; de Jong, D.J.; Diavatopoulos, D.A.; Hermans, P.W.; Ferwerda, G. Respiratory syncytial virus infection augments NOD2 signaling in an IFN-beta-dependent manner in human primary cells. Eur. J. Immunol. 2012, 42, 2727–2735, doi:10.1002/eji.201242396.
[170]
Ling, Z.; Tran, K.C.; Teng, M.N. Human respiratory syncytial virus nonstructural protein NS2 antagonizes the activation of beta interferon transcription by interacting with RIG-I. J. Virol. 2009, 83, 3734–3742, doi:10.1128/JVI.02434-08.
[171]
Boyapalle, S.; Wong, T.; Garay, J.; Teng, M.; San Juan-Vergara, H.; Mohapatra, S.; Mohapatra, S. Respiratory syncytial virus NS1 protein colocalizes with mitochondrial antiviral signaling protein MAVS following infection. PLoS One 2012, 7, e29386.
[172]
Lifland, A.W.; Jung, J.; Alonas, E.; Zurla, C.; Crowe, J.E.; Santangelo, P.J. Human respiratory syncytial virus nucleoprotein and inclusion bodies antagonize the innate immune response mediated by MDA5 and MAVS. J. Virol. 2012, 86, 8245–8258, doi:10.1128/JVI.00215-12.
[173]
Banos-Lara, Mdel.R.; Ghosh, A.; Guerrero-Plata, A. Critical role of MDA5 in the interferon response induced by human metapneumovirus infection in dendritic cells and in vivo. J. Virol. 2013, 87, 1242–1251, doi:10.1128/JVI.01213-12.
[174]
Bao, X.; Liu, T.; Shan, Y.; Li, K.; Garofalo, R.P.; Casola, A. Human metapneumovirus glycoprotein G inhibits innate immune responses. PLoS. Pathog. 2008, 4, e1000077, doi:10.1371/journal.ppat.1000077.
[175]
Ren, J.; Wang, Q.; Kolli, D.; Prusak, D.J.; Tseng, C.T.; Chen, Z.J.; Li, K.; Wood, T.G.; Bao, X. Human metapneumovirus M2–2 protein inhibits innate cellular signaling by targeting MAVS. J. Virol. 2012, 86, 13049–13061.
[176]
Bao, X.; Kolli, D.; Ren, J.; Liu, T.; Garofalo, R.P.; Casola, A. Human metapneumovirus glycoprotein g disrupts mitochondrial signaling in airway epithelial cells. PLoS One 2013. Accepted.
[177]
Inohara; Chamaillard; McDonald, C.; Nunez, G. NOD-LRR proteins: Role in host-microbial interactions and inflammatory disease. Annu. Rev. Biochem. 2005, 74, 355–383.
[178]
Kufer, T.A.; Fritz, J.H.; Philpott, D.J. NACHT-LRR proteins (NLRs) in bacterial infection and immunity. Trends Microbiol. 2005, 13, 381–388, doi:10.1016/j.tim.2005.06.004.
[179]
Harton, J.A.; Linhoff, M.W.; Zhang, J.; Ting, J.P. Cutting edge: CATERPILLER: A large family of mammalian genes containing CARD, pyrin, nucleotide-binding, and leucine-rich repeat domains. J. Immunol. 2002, 169, 4088–4093.
[180]
Ting, J.P.; Lovering, R.C.; Alnemri, E.S.; Bertin, J.; Boss, J.M.; Davis, B.K.; Flavell, R.A.; Girardin, S.E.; Godzik, A.; Harton, J.A.; et al. The NLR gene family: A standard nomenclature. Immunity 2008, 28, 285–287, doi:10.1016/j.immuni.2008.02.005.
[181]
Ting, J.P.; Davis, B.K. CATERPILLER: A novel gene family important in immunity, cell death, and diseases. Annu. Rev. Immunol. 2005, 23, 387–414, doi:10.1146/annurev.immunol.23.021704.115616.
[182]
Chen, G.; Shaw, M.H.; Kim, Y.G.; Nunez, G. NOD-Like receptors: Role in innate immunity and inflammatory disease. Annu. Rev. Pathol. 2009, 4, 365–398, doi:10.1146/annurev.pathol.4.110807.092239.
[183]
Ye, Z.; Ting, J.P.-Y. NLR, the nucleotide-binding domain leucine-rich repeat containing gene family. Curr. Opin. Immunol. 2008, 20, 3–9.
[184]
Pauleau, A.L.; Murray, P.J. Role of Nod2 in the response of macrophages to toll-like receptor agonists. Mol. Cell Biol. 2003, 23, 7531–7539, doi:10.1128/MCB.23.21.7531-7539.2003.
[185]
Girardin, S.E.; Tournebize, R.; Mavris, M.; Page, A.L.; Li, X.; Stark, G.R.; Bertin, J.; DiStefano, P.S.; Yaniv, M.; Sansonetti, P.J.; et al. CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO Rep. 2001, 2, 736–742.
[186]
Martinon, F.; Burns, K.; Tschopp, J. The Inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proil-beta. Mol. Cell 2002, 10, 417–426, doi:10.1016/S1097-2765(02)00599-3.
[187]
Srinivasula, S.M.; Poyet, J.L.; Razmara, M.; Datta, P.; Zhang, Z.; Alnemri, E.S. The PYRIN-CARD protein ASC is an activating adaptor for Caspase-1. J. Biol. Chem. 2002, 277, 21119–21122.
Kanneganti, T.D.; Body-Malapel, M.; Amer, A.; Park, J.H.; Whitfield, J.; Franchi, L.; Taraporewala, Z.F.; Miller, D.; Patton, J.T.; Inohara, N.; et al. Critical role for Cryopyrin/Nalp3 in activation of Caspase-1 in response to viral infection and double-stranded RNA. J. Biol. Chem. 2006, 281, 36560–36568, doi:10.1074/jbc.M607594200.
[190]
Bruey, J.M.; Bruey-Sedano, N.; Newman, R.; Chandler, S.; Stehlik, C.; Reed, J.C. PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages. J. Biol. Chem. 2004, 279, 51897–51907.
[191]
Conti, B.J.; Davis, B.K.; Zhang, J.; O'Connor, W.; Williams, K.L.; Ting, J.P.Y. CATERPILLER 16.2 (CLR16.2), a Novel NBD/LRR family member that negatively regulates T cell function. J. Biol. Chem. 2005, 280, 18375–18385.
[192]
Lich, J.D.; Williams, K.L.; Moore, C.B.; Arthur, J.C.; Davis, B.K.; Taxman, D.J.; Ting, J.P. Monarch-1 suppresses non-canonical NF-kappaB activation and p52-dependent chemokine expression in monocytes. J. Immunol. 2007, 178, 1256–1260.
[193]
Masumoto, J.; Dowds, T.A.; Schaner, P.; Chen, F.F.; Ogura, Y.; Li, M.; Zhu, L.; Katsuyama, T.; Sagara, J.; Taniguchi, S.; et al. ASC is an activating adaptor for NF-+|B and caspase-8-dependent apoptosis. Biochem. Biophys. Res. Commun. 2003, 303, 69–73, doi:10.1016/S0006-291X(03)00309-7.
[194]
Mariathasan, S.; Newton, K.; Monack, D.M.; Vucic, D.; French, D.M.; Lee, W.P.; Roose-Girma, M.; Erickson, S.; Dixit, V.M. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 2004, 430, 213–218.
[195]
Chen, G.; Pedra, J.H. The inflammasome in host defense. Sensors (Basel) 2010, 10, 97–111.
[196]
Masumoto, J.; Yang, K.; Varambally, S.; Hasegawa, M.; Tomlins, S.A.; Qiu, S.; Fujimoto, Y.; Kawasaki, A.; Foster, S.J.; Horie, Y.; et al. Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo. J. Exp. Med. 2006, 203, 203–213.
[197]
Allen, I.C.; Scull, M.A.; Moore, C.B.; Holl, E.K.; McElvania-TeKippe, E.; Taxman, D.J.; Guthrie, E.H.; Pickles, R.J.; Ting, J.P.Y. The NLRP3 inflammasome mediates in vivo innate immunity to influenza a virus through recognition of viral RNA. Immunity 2009, 30, 556–565, doi:10.1016/j.immuni.2009.02.005.
[198]
Kanneganti, T.D. Central roles of NLRs and inflammasomes in viral infection. Nat. Rev. Immunol. 2010, 10, 688–698, doi:10.1038/nri2851.
[199]
Takeuchi, R.; Tsutsumi, H.; Osaki, M.; Sone, S.; Imai, S.; Chiba, S. Respiratory syncytial virus infection of neonatal monocytes stimulates synthesis of interferon regulatory factor 1 and interleukin-1beta (IL-1beta)-converting enzyme and secretion of IL-1beta. J. Virol. 1998, 72, 837–840.
[200]
Shafique, M.; Wilschut, J.; de Haan, A. Induction of mucosal and systemic immunity against respiratory syncytial virus by inactivated virus supplemented with TLR9 and NOD2 ligands. Vaccine 2012, 30, 597–606, doi:10.1016/j.vaccine.2011.11.054.
