O tratamento para BVA causada pelo VSR é limitado e consiste apenas no suporte à doença causado pela infecção. Existe apenas uma terapia específica disponível hoje em dia capaz de prevenir o desenvolvimento da doença. A eficácia do anticorpo monoclonal palavizumabe mostra que altos níveis de anticorpos circulantes são suficientes à proteção contra a doença de trato respiratório inferior em neonatos (7).
O uso de proteínas específicas do vírus pode ser de grande importância no desenvolvimento de novas estratégias profiláticas contra o VSR. No momento, diversos grupos de pesquisa têm trabalhado com a proteína G do VSR, e os resultados iniciais são bastante animadores, já que alguns estudos experimentais têm demonstrado que a vacinação com polipeptídeos derivados de regiões centrais da proteína G reduzem a replicação viral e a inflamação pulmonar em camundongos (49).
CONCLUSÃO
Embora nas últimas décadas tenham ocorrido avanços no entendimento dos mecanismos de ação do VSR, diversas limitações ainda estão presentes. Pode-se observar que existe uma diferença na resposta causada pelo vírus, quando comparados estudos experimentais e clínicos, e estas diferenças devem ser levadas
Artigo de Revisão
41em consideração na tentativa de desenvolver uma nova terapia ou vacina contra o vírus.
Dois potenciais alvos terapêuticos são citocinas e proteínas isoladas do vírus. O bloqueio de certas citocinas ou quimiocinas poderia ser usado para reduzir a doença pulmonar causada pelo VSR. A administração de anticorpos que bloqueiam a atividade de certas citocinas, in vivo, como RANTES e CCL20, tem demonstrado redução significativa na hiperresposividade das vias aéreas em camundongos e previne a produção excessiva de muco pelas células epiteliais. Proteínas isoladas do vírus, como a proteína G, vem sendo cada vez mais estudadas no desenvolvimento de uma vacina eficaz contra o VSR.
REFERÊNCIAS
1. Blount RE, Jr., Morris JA, Savage RE. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med. 1956 Jul;92(3):544-9.
2. 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 Nov;66(3):291-300.
3. Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis- associated hospitalizations among US children, 1980-1996. JAMA. 1999 Oct 20;282(15):1440-6.
4. Hall CB, Long CE, Schnabel KC. Respiratory syncytial virus infections in previously healthy working adults. Clin Infect Dis. 2001 Sep 15;33(6):792-6.
5. Paramore LC, Ciuryla V, Ciesla G, Liu L. Economic impact of respiratory syncytial virus-related illness in the US: an analysis of national databases.
Pharmacoeconomics. 2004;22(5):275-84.
6. Collins PL, Graham BS. Viral and host factors in human respiratory syncytial virus pathogenesis. J Virol. 2008 Mar;82(5):2040-55.
7. Habibi MS, Openshaw PJ. Benefit and harm from immunity to respiratory syncytial virus: implications for treatment. Curr Opin Infect Dis. 2012 Dec;25(6):687-94.
Artigo de Revisão
428. Spann KM, Tran KC, Chi B, Rabin RL, Collins PL. Suppression of the induction of alpha, beta, and lambda interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages [corrected]. J Virol. 2004 Apr;78(8):4363-9.
9. Hendry RM, Talis AL, Godfrey E, Anderson LJ, Fernie BF, McIntosh K. Concurrent circulation of antigenically distinct strains of respiratory syncytial virus during community outbreaks. J Infect Dis. 1986 Feb;153(2):291-7.
10. Kwilas S, Liesman RM, Zhang L, Walsh E, Pickles RJ, Peeples ME. Respiratory syncytial virus grown in Vero cells contains a truncated attachment protein that alters its infectivity and dependence on glycosaminoglycans. J Virol. 2009
Oct;83(20):10710-8.
11. Tayyari F, Marchant D, Moraes TJ, Duan W, Mastrangelo P, Hegele RG.
Identification of nucleolin as a cellular receptor for human respiratory syncytial virus. Nat Med. 2011 Sep;17(9):1132-5.
12. Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986 Jun;140(6):543-6.
13. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010 May
1;375(9725):1545-55.
14. Straliotto SM, Nestor SM, Siqueira MM. Respiratory syncytial virus groups A and B in Porto Alegre, Brazil, from 1990 to 1995 and 1998. Mem Inst Oswaldo Cruz. 2001 Feb;96(2):155-8.
15. D'Elia C, Siqueira MM, Portes SA, Sant'Anna CC. [Respiratory syncytial virus -- associated lower respiratory tract infections in hospitalized infants]. Rev Soc Bras Med Trop. 2005 Jan-Feb;38(1):7-10.
16. Bloemers BL, van Furth AM, Weijerman ME, Gemke RJ, Broers CJ, van den Ende K, et al. Down syndrome: a novel risk factor for respiratory syncytial virus bronchiolitis--a prospective birth-cohort study. Pediatrics. 2007 Oct;120(4):e1076-81.
17. Garcia CG, Bhore R, Soriano-Fallas A, Trost M, Chason R, Ramilo O, et al. Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics. 2010 Dec;126(6):e1453-60.
18. Simoes EA. Respiratory syncytial virus infection. Lancet. 1999 Sep 4;354(9181):847- 52.
19. Smyth RL, Openshaw PJ. Bronchiolitis. Lancet. 2006 Jul 22;368(9532):312-22. 20. Liu P, Jamaluddin M, Li K, Garofalo RP, Casola A, Brasier AR. 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
Feb;81(3):1401-11.
21. Xie XH, Law HK, Wang LJ, Li X, Yang XQ, Liu EM. Lipopolysaccharide induces IL-6 production in respiratory syncytial virus-infected airway epithelial cells through the toll- like receptor 4 signaling pathway. Pediatr Res. 2009 Feb;65(2):156-62.
Artigo de Revisão
4322. Groskreutz DJ, Monick MM, Powers LS, Yarovinsky TO, Look DC, Hunninghake GW. Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells. J Immunol. 2006 Feb 1;176(3):1733-40.
23. Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P, Weber F, et al. RIG-I-
mediated antiviral responses to single-stranded RNA bearing 5'-phosphates. Science. 2006 Nov 10;314(5801):997-1001.
24. Jewell NA, Vaghefi N, Mertz SE, Akter P, Peebles RS, Jr., Bakaletz LO, et al. Differential type I interferon induction by respiratory syncytial virus and influenza a virus in vivo. J Virol. 2007 Sep;81(18):9790-800.
25. Murawski MR, Bowen GN, Cerny AM, Anderson LJ, Haynes LM, Tripp RA, et al. Respiratory syncytial virus activates innate immunity through Toll-like receptor 2. J Virol. 2009 Feb;83(3):1492-500.
26. Scagnolari C, Midulla F, Pierangeli A, Moretti C, Bonci E, Berardi R, 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 Jun;16(6):816-23.
27. Monick MM, Yarovinsky TO, Powers LS, Butler NS, Carter AB, Gudmundsson G, et al. Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin. J Biol Chem. 2003 Dec 26;278(52):53035-44.
28. Wheeler DS, Chase MA, Senft AP, Poynter SE, Wong HR, Page K. Extracellular Hsp72, an endogenous DAMP, is released by virally infected airway epithelial cells and activates neutrophils via Toll-like receptor (TLR)-4. Respir Res. 2009;10:31. 29. Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, et al. Pattern
recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000 Nov;1(5):398-401.
30. Gagro A, Tominac M, Krsulovic-Hresic V, Bace A, Matic M, Drazenovic V, et al. Increased Toll-like receptor 4 expression in infants with respiratory syncytial virus bronchiolitis. Clin Exp Immunol. 2004 Feb;135(2):267-72.
31. Haynes LM, Moore DD, Kurt-Jones EA, Finberg RW, Anderson LJ, Tripp RA. Involvement of toll-like receptor 4 in innate immunity to respiratory syncytial virus. J Virol. 2001 Nov;75(22):10730-7.
32. Douville RN, Lissitsyn Y, Hirschfeld AF, Becker AB, Kozyrskyj AL, Liem J, et al. TLR4 Asp299Gly and Thr399Ile polymorphisms: no impact on human immune
responsiveness to LPS or respiratory syncytial virus. PLoS One. 2010;5(8):e12087. 33. Kresfelder TL, Janssen R, Bont L, Pretorius M, 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 Oct;83(10):1834-40.
34. 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
Artigo de Revisão
4435. Schlender J, Hornung V, Finke S, Gunthner-Biller M, Marozin S, Brzozka K, et al. Inhibition of toll-like receptor 7- and 9-mediated alpha/beta interferon production in human plasmacytoid dendritic cells by respiratory syncytial virus and measles virus. J Virol. 2005 May;79(9):5507-15.
36. Lukacs NW, Smit JJ, Mukherjee S, Morris SB, Nunez G, Lindell DM. Respiratory virus-induced TLR7 activation controls IL-17-associated increased mucus via IL-23 regulation. J Immunol. 2010 Aug 15;185(4):2231-9.
37. Johnson TR, Rao S, Seder RA, Chen M, Graham BS. 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 May 18;27(23):3045-52.
38. Senft AP, Taylor RH, Lei W, Campbell SA, Tipper JL, Martinez MJ, et al. Respiratory syncytial virus impairs macrophage IFN-alpha/beta- and IFN-gamma-stimulated transcription by distinct mechanisms. Am J Respir Cell Mol Biol. 2010 Apr;42(4):404- 14.
39. Bueno SM, Gonzalez PA, Riedel CA, Carreno LJ, Vasquez AE, Kalergis AM. Local cytokine response upon respiratory syncytial virus infection. Immunol Lett. 2011 May;136(2):122-9.
40. Haeberle HA, Takizawa R, Casola A, Brasier AR, Dieterich HJ, Van Rooijen N, et al. Respiratory syncytial virus-induced activation of nuclear factor-kappaB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways. J Infect Dis. 2002 Nov 1;186(9):1199-206.
41. Rudd BD, Schaller MA, Smit JJ, Kunkel SL, Neupane R, Kelley L, et al. MyD88- mediated instructive signals in dendritic cells regulate pulmonary immune responses during respiratory virus infection. J Immunol. 2007 May 1;178(9):5820-7.
42. Lee DC, Harker JA, Tregoning JS, Atabani SF, Johansson C, Schwarze J, et al. CD25+ natural regulatory T cells are critical in limiting innate and adaptive immunity and resolving disease following respiratory syncytial virus infection. J Virol. 2010 Sep;84(17):8790-8.
43. Yoboua F, Martel A, Duval A, Mukawera E, Grandvaux N. Respiratory syncytial virus- mediated NF-kappa B p65 phosphorylation at serine 536 is dependent on RIG-I, TRAF6, and IKK beta. J Virol. 2010 Jul;84(14):7267-77.
44. Cautivo KM, Bueno SM, Cortes CM, Wozniak A, Riedel CA, Kalergis AM. Efficient lung recruitment of respiratory syncytial virus-specific Th1 cells induced by
recombinant bacillus Calmette-Guerin promotes virus clearance and protects from infection. J Immunol. 2010 Dec 15;185(12):7633-45.
45. Janssen R, Bont L, Siezen CL, Hodemaekers HM, Ermers MJ, Doornbos G, et al. Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J Infect Dis. 2007 Sep 15;196(6):826-34. 46. Langedijk JP, de Groot BL, Berendsen HJ, van Oirschot JT. Structural homology of
the central conserved region of the attachment protein G of respiratory syncytial virus with the fourth subdomain of 55-kDa tumor necrosis factor receptor. Virology. 1998 Apr 10;243(2):293-302.
Artigo de Revisão
4547. Tripp RA, Jones LP, Haynes LM, Zheng H, Murphy PM, Anderson LJ. CX3C
chemokine mimicry by respiratory syncytial virus G glycoprotein. Nat Immunol. 2001 Aug;2(8):732-8.
48. Amanatidou V, Sourvinos G, Apostolakis S, Tsilimigaki A, Spandidos DA. T280M variation of the CX3C receptor gene is associated with increased risk for severe respiratory syncytial virus bronchiolitis. Pediatr Infect Dis J. 2006 May;25(5):410-4. 49. Zhang W, Choi Y, Haynes LM, Harcourt JL, Anderson LJ, Jones LP, et al.
Vaccination to induce antibodies blocking the CX3C-CX3CR1 interaction of respiratory syncytial virus G protein reduces pulmonary inflammation and virus replication in mice. J Virol. 2010 Jan;84(2):1148-57.
50. McNamara PS, Flanagan BF, Hart CA, Smyth RL. Production of chemokines in the lungs of infants with severe respiratory syncytial virus bronchiolitis. J Infect Dis. 2005 Apr 15;191(8):1225-32.
51. Noah TL, Becker S. Chemokines in nasal secretions of normal adults experimentally infected with respiratory syncytial virus. Clin Immunol. 2000 Oct;97(1):43-9.
52. van Benten IJ, van Drunen CM, Koevoet JL, Koopman LP, Hop WC, Osterhaus AD, et al. Reduced nasal IL-10 and enhanced TNFalpha responses during rhinovirus and RSV-induced upper respiratory tract infection in atopic and non-atopic infants. J Med Virol. 2005 Feb;75(2):348-57.
53. Puthothu B, Bierbaum S, Kopp MV, Forster J, Heinze J, Weckmann M, et al. Association of TNF-alpha with severe respiratory syncytial virus infection and bronchial asthma. Pediatr Allergy Immunol. 2009 Mar;20(2):157-63.
54. Smyth RL, Mobbs KJ, O'Hea U, Ashby D, Hart CA. Respiratory syncytial virus bronchiolitis: disease severity, interleukin-8, and virus genotype. Pediatr Pulmonol. 2002 May;33(5):339-46.
55. Johnson JE, Gonzales RA, Olson SJ, Wright PF, Graham BS. The histopathology of fatal untreated human respiratory syncytial virus infection. Mod Pathol. 2007
Jan;20(1):108-19.
56. Sow FB, Gallup JM, Krishnan S, Patera AC, Suzich J, Ackermann MR. Respiratory syncytial virus infection is associated with an altered innate immunity and a
heightened pro-inflammatory response in the lungs of preterm lambs. Respir Res. 2011;12:106.
57. Assefa D, Amin N, Dozor AJ, Parton LA. Attenuated interleukin-8/leukocyte immunoresponse in preterm infants compared with term infants hospitalized with respiratory syncytial virus bronchiolitis: a pilot study. Hum Immunol. 2011
Sep;72(9):708-11.
58. Lotz MT, Peebles RS, Jr. Mechanisms of respiratory syncytial virus modulation of airway immune responses. Curr Allergy Asthma Rep. 2012 Oct;12(5):380-7. 59. Garcia-Sastre A, Biron CA. Type 1 interferons and the virus-host relationship: a
lesson in detente. Science. 2006 May 12;312(5775):879-82.
60. Li Z, Strunk JJ, Lamken P, Piehler J, Walz T. The EM structure of a type I interferon- receptor complex reveals a novel mechanism for cytokine signaling. J Mol Biol. 2008 Mar 28;377(3):715-24.
Artigo de Revisão
4661. Claudinon J, Gonnord P, Beslard E, Marchetti M, Mitchell K, Boularan C, et al.
Palmitoylation of interferon-alpha (IFN-alpha) receptor subunit IFNAR1 is required for the activation of Stat1 and Stat2 by IFN-alpha. J Biol Chem. 2009 Sep
4;284(36):24328-40.
62. Pala P, Bjarnason R, Sigurbergsson F, Metcalfe C, Sigurs N, Openshaw PJ. Enhanced IL-4 responses in children with a history of respiratory syncytial virus bronchiolitis in infancy. Eur Respir J. 2002 Aug;20(2):376-82.
63. Hussell T, Openshaw PJ. Intracellular IFN-gamma expression in natural killer cells precedes lung CD8+ T cell recruitment during respiratory syncytial virus infection. J Gen Virol. 1998 Nov;79 ( Pt 11):2593-601.
64. Hussell T, Openshaw PJ. IL-12-activated NK cells reduce lung eosinophilia to the attachment protein of respiratory syncytial virus but do not enhance the severity of illness in CD8 T cell-immunodeficient conditions. J Immunol. 2000 Dec
15;165(12):7109-15.
65. Kaiko GE, Phipps S, Angkasekwinai P, Dong C, Foster PS. NK cell deficiency predisposes to viral-induced Th2-type allergic inflammation via epithelial-derived IL- 25. J Immunol. 2010 Oct 15;185(8):4681-90.
66. Beyer M, Bartz H, Horner K, Doths S, Koerner-Rettberg C, Schwarze J. Sustained increases in numbers of pulmonary dendritic cells after respiratory syncytial virus infection. J Allergy Clin Immunol. 2004 Jan;113(1):127-33.
67. Smit JJ, Rudd BD, Lukacs NW. Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus. J Exp Med. 2006 May 15;203(5):1153-9.
68. Openshaw PJ. Flow cytometric analysis of pulmonary lymphocytes from mice infected with respiratory syncytial virus. Clin Exp Immunol. 1989 Feb;75(2):324-8.
69. Cannon MJ, Openshaw PJ, Askonas BA. Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. J Exp Med. 1988 Sep 1;168(3):1163-8.
70. Connors M, Kulkarni AB, Firestone CY, Holmes KL, Morse HC, 3rd, Sotnikov AV, et al. Pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of CD4+ T cells. J Virol. 1992 Dec;66(12):7444-51.
71. Connors M, Giese NA, Kulkarni AB, Firestone CY, Morse HC, 3rd, Murphy BR. Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10. J Virol. 1994 Aug;68(8):5321-5. 72. Roman M, Calhoun WJ, Hinton KL, Avendano LF, Simon V, Escobar AM, et al.
Respiratory syncytial virus infection in infants is associated with predominant Th-2- like response. Am J Respir Crit Care Med. 1997 Jul;156(1):190-5.
73. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JT, et al. Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis. Eur Respir J. 1999 Jul;14(1):144-9.
Artigo de Revisão
4774. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JM, et al. Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. J Infect Dis. 2001 Aug 1;184(3):355-8. 75. Chen ZM, Mao JH, Du LZ, Tang YM. Association of cytokine responses with disease
severity in infants with respiratory syncytial virus infection. Acta Paediatr. 2002;91(9):914-22.
76. Heidema J, Lukens MV, van Maren WW, van Dijk ME, Otten HG, van Vught AJ, et al. CD8+ T cell responses in bronchoalveolar lavage fluid and peripheral blood
mononuclear cells of infants with severe primary respiratory syncytial virus infections. J Immunol. 2007 Dec 15;179(12):8410-7.
77. Lukens MV, van de Pol AC, Coenjaerts FE, Jansen NJ, Kamp VM, Kimpen JL, et al. A systemic neutrophil response precedes robust CD8(+) T-cell activation during natural respiratory syncytial virus infection in infants. J Virol. 2010 Mar;84(5):2374-83. 78. Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of
CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005 Nov;6(11):1133-41.
79. Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, et al. Phenotypic and functional features of human Th17 cells. J Exp Med. 2007 Aug 6;204(8):1849-61.
80. Mukherjee S, Lindell DM, Berlin AA, Morris SB, Shanley TP, Hershenson MB, et al. IL-17-induced pulmonary pathogenesis during respiratory viral infection and
exacerbation of allergic disease. Am J Pathol. 2011 Jul;179(1):248-58.
81. Bera MM, Lu B, Martin TR, Cui S, Rhein LM, Gerard C, et al. Th17 cytokines are critical for respiratory syncytial virus-associated airway hyperreponsiveness through regulation by complement C3a and tachykinins. J Immunol. 2011 Oct 15;187(8):4245- 55.
82. Faber TE, Groen H, Welfing M, Jansen KJ, Bont LJ. Specific increase in local IL-17 production during recovery from primary RSV bronchiolitis. J Med Virol. 2012 Jul;84(7):1084-8.
83. Ruckwardt TJ, Bonaparte KL, Nason MC, Graham BS. Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities. J Virol. 2009 Apr;83(7):3019-28. 84. Loebbermann J, Thornton H, Durant L, Sparwasser T, Webster KE, Sprent J, et al.
Regulatory T cells expressing granzyme B play a critical role in controlling lung inflammation during acute viral infection. Mucosal Immunol. 2012 Mar;5(2):161-72. 85. Bartz H, Buning-Pfaue F, Turkel O, Schauer U. Respiratory syncytial virus induces prostaglandin E2, IL-10 and IL-11 generation in antigen presenting cells. Clin Exp Immunol. 2002 Sep;129(3):438-45.
86. Grissell TV, Powell H, Shafren DR, Boyle MJ, Hensley MJ, Jones PD, et al.
Interleukin-10 gene expression in acute virus-induced asthma. Am J Respir Crit Care Med. 2005 Aug 15;172(4):433-9.
87. Jartti T, Paul-Anttila M, Lehtinen P, Parikka V, Vuorinen T, Simell O, et al. Systemic T-helper and T-regulatory cell type cytokine responses in rhinovirus vs. respiratory
Artigo de Revisão
48syncytial virus induced early wheezing: an observational study. Respir Res. 2009;10:85.
88. Stevens WW, Sun J, Castillo JP, Braciale TJ. Pulmonary eosinophilia is attenuated by early responding CD8(+) memory T cells in a murine model of RSV vaccine-
enhanced disease. Viral Immunol. 2009 Jul;22(4):243-51.
89. Vieira RA, Diniz EM, Ceccon ME. Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity. J Bras Pneumol. 2010 Jan-Feb;36(1):59-66.
90. Stokes KL, Chi MH, Sakamoto K, Newcomb DC, Currier MG, Huckabee MM, et al. Differential pathogenesis of respiratory syncytial virus clinical isolates in BALB/c mice. J Virol. 2011 Jun;85(12):5782-93.
49