Advertisement

Current Concepts of the Pathogenesis of RSV Bronchiolitis

  • Louis Bont
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 634)

Introduction

The respiratory syncytial virus (RSV) is a member of the Pneumovirus genus within the family Paramyxoviridae. The RSV has a 15-kb-long, single-stranded, negative-sense RNA genome, encoding 11 genes. These include the immunodominant attachment-(G) and fusion (F) proteins at the surface of the virion and the matrix (M) protein and the immunomodulatory non-structural (NS1/NS2) proteins.

RSV bronchiolitis is the leading cause of infant hospitalization during the winter season. It is not known why RSV infections do not occur during the summer. There is evidence that the incidence of RSV infections is increased during periods of low ultraviolet B radiance (Yusuf et al., 2007). Practically all children are infected with RSV before the age of 2 years, but only a minority develop severe disease requiring hospital admission. It is estimated that 10% of infants hospitalized for RSV require mechanical ventilation (Bont and Kimpen, 2002; Simoes, 1999; Smyth and Openshaw, 2006). With...

Keywords

Respiratory Syncytial Virus Innate Immune System Single Nucleotide Polymorphism Respiratory Syncytial Virus Infection Severe Respiratory Syncytial Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Aberle, J. H., Aberle, S. W., Dworzak, M. N., Mandl, C. W., Rebhandl, W., Vollnhofer, G., Kundi, M., and Popow-Kraupp, T. (1999). Reduced Interferon-gamma expression in peripheral blood mononuclear cells of infants with severe respiratory syncytial virus disease. Am. J. Respir. Crit. Care Med. 160, 1263–1268.PubMedGoogle Scholar
  2. Adkins, B., Leclerc, C., and Marshall-Clarke, S. (2004). Neonatal adaptive immunity comes of age. Nat. Rev. Immunol. 4, 553–564.PubMedCrossRefGoogle Scholar
  3. Awomoyi, A. A., Rallabhandi, P., Pollin, T. I., Lorenz, E., Sztein, M. B., Boukhvalova, M. S., Hemming, V. G., Blanco, J. C., and Vogel, S. N. (2007). Association of TLR4 Polymorphisms with Symptomatic Respiratory Syncytial Virus Infection in High-Risk Infants and Young Children. J. Immunol. 179, 3171–3177.PubMedGoogle Scholar
  4. Bendelja, K., Gagro, A., Bace, A., Lokar-Kolbas, R., Krsulovic-Hresic, V., Drazenovic, V., Mlinaric-Galinovic, G., and Rabatic, S. (2000). Predominant type-2 response in infants with respiratory syncytial virus (RSV) infection demonstrated by cytokine flow cytometry. Clin. Exp. Immunol. 121, 332–338.PubMedCrossRefGoogle Scholar
  5. Bloemers, B., Furth v, A. M., Weijerman, M., Broers, C., Gemke, R. J. B. J., Strengers, J. L. M., Kimpen, J. L. L., and Bont, L. (2007). Increased incidence of respiratory syncytial virus lower respiratory hospitalisation in children with Down syndrome. Pediatrics. 121(4), e1076–1081.Google Scholar
  6. Bont, L., Aalderen, v. W. M. C., and Kimpen, J. L. L. (2000). Long-term consequences of respiratory syncytial virus (RSV) bronchiolitis. Paediatr. Respir. Rev. 1, 221–227.PubMedCrossRefGoogle Scholar
  7. Bont, L., Heijnen, C. J., Kavelaars, A., van Aalderen, W. M., Brus, F., Draaisma, J. M., Pekelharing-Berghuis, M., Diemen-Steenvoorde, R. A., and Kimpen, J. L. (2001). Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. J. Infect. Dis. 184, 355–358.PubMedCrossRefGoogle Scholar
  8. Bont, L., Kavelaars, A., Heijnen, C. J., van Vught, A. J., and Kimpen, J. L. (2000b). Monocyte interleukin-12 production is inversely related to duration of respiratory failure in respiratory syncytial virus bronchiolitis. J. Infect. Dis. 181, 1772–1775.Google Scholar
  9. Bont, L. and Kimpen, J. L. (2002). Immunological mechanisms of severe respiratory syncytial virus bronchiolitis. Intensive Care Med. 28, 616–621.PubMedCrossRefGoogle Scholar
  10. Cannon, M. J., Openshaw, P. J. M., and Askonas, B. A. (1988). Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. J. Exp. Med. 168, 1163–1168.PubMedCrossRefGoogle Scholar
  11. Chang, J. and Braciale, T. J. (2002). Respiratory syncytial virus infection suppresses lung CD8+ T-cell effector activity and peripheral CD8+ T-cell memory in the respiratory tract. Nat. Med. 8, 54–60.PubMedCrossRefGoogle Scholar
  12. Choi, E. H., Lee, H. J., Yoo, T., and Chanock, S. J. (2002). A common haplotype of interleukin-4 gene IL4 is associated with severe respiratory syncytial virus disease in Korean children. J. Infect. Dis. 186, 1207–1211.PubMedCrossRefGoogle Scholar
  13. Copenhaver, C. C., Gern, J. E., Li, Z., Shult, P. A., Rosenthal, L. A., Mikus, L. D., Kirk, C. J., Roberg, K. A., Anderson, E. L., Tisler, C. J., DaSilva, D. F., Hiemke, H. J., Gentile, K., Gangnon, R. E., and Lemanske, R. F., Jr. (2004). Cytokine response patterns, exposure to viruses, and respiratory infections in the first year of life. Am J Respir. Crit Care Med. 170, 175–180.PubMedCrossRefGoogle Scholar
  14. de Graaff, P. M., de Jong, E. C., van Capel, T. M., van Dijk, M. E., Roholl, P. J., Boes, J., Luytjes, W., Kimpen, J. L., and van Bleek, G. M. (2005). Respiratory syncytial virus infection of monocyte-derived dendritic cells decreases their capacity to activate CD4 T cells. J. Immunol. 175, 5904–5911.PubMedGoogle Scholar
  15. Ermers, M. J., Hoebee, B., Hodemaekers, H. M., Kimman, T. G., Kimpen, J. L., and Bont, L. (2007). IL-13 genetic polymorphism identifies children with late wheezing after respiratory syncytial virus infection. J. Allergy Clin. Immunol. 119(5), 1086–1091.Google Scholar
  16. Feltes, T. F., Cabalka, A. K., Meissner, H. C., Piazza, F. M., Carlin, D. A., Top, F. H., Jr., Connor, E. M., and Sondheimer, H. M. (2003). Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J. Pediatr. 143, 532–540.PubMedCrossRefGoogle Scholar
  17. Garofalo, R. P., Mei, F., Espejeo, R., Ye, G., Haeberle, H., Baron, S., Ogra, P. L., and Reyes, V. E. (1996). Respiratory syncytial virus infection of human respiratory epithelial cells up-regulates class 1 MHC Expression through the induction of IFN-beta and IL-1-alpha. J. Immunol. 157, 2506–2513.PubMedGoogle Scholar
  18. Gern, J. E., Brooks, G. D., Meyer, P., Chang, A., Shen, K., Evans, M. D., Tisler, C., Dasilva, D., Roberg, K. A., Mikus, L. D., Rosenthal, L. A., Kirk, C. J., Shult, P. A., Bhattacharya, A., Li, Z., Gangnon, R., and Lemanske, R. F., Jr. (2006). Bidirectional interactions between viral respiratory illnesses and cytokine responses in the first year of life. J Allergy Clin. Immunol. 117, 72–78.PubMedCrossRefGoogle Scholar
  19. Goetghebuer, T., Isles, K., Moore, C., Thomson, A., Kwiatkowski, D., and Hull, J. (2004). Genetic predisposition to wheeze following respiratory syncytial virus bronchiolitis. Clin. Exp. Allergy 34, 801–803.PubMedCrossRefGoogle Scholar
  20. Graham, B. S., Bunton, L. A., Wright, P. F., and Karzon, D. T. (1991). Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. J. Clin. Invest. 88, 1026–1033.PubMedCrossRefGoogle Scholar
  21. Graham, B. S., Johnson, T. R., and Peebles, R. S. (2000). Immune-mediated disease pathogenesis in respiratory syncytial virus infection. Immunopharmacology 48, 237–247.PubMedCrossRefGoogle Scholar
  22. Graham, B. S., Perkins, M. D., Wright, P. F., and Karzon, D. T. (1988). Primary respiratory syncytial virus infection in mice. J. Med. Virol. 26, 153–162.PubMedCrossRefGoogle Scholar
  23. Haland, G., Carlsen, K. C., Sandvik, L., Devulapalli, C. S., Munthe-Kaas, M. C., Pettersen, M., and Carlsen, K. H. (2006). Reduced lung function at birth and the risk of asthma at 10 years of age. N. Engl. J. Med. 355, 1682–1689.PubMedCrossRefGoogle Scholar
  24. Hoebee, B., Rietveld, E., Bont, L., Oosten, M., Hodemaekers, H. M., Nagelkerke, N. J., Neijens, H. J., Kimpen, J. L., and Kimman, T. G. (2003). Association of severe respiratory syncytial virus bronchiolitis with interleukin-4 and interleukin-4 receptor alpha polymorphisms. J. Infect. Dis. 187, 2–11.PubMedCrossRefGoogle Scholar
  25. Hull, J., Thomson, A., and Kwiatkowski, D. (2000). Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax 55, 1023–1027.PubMedCrossRefGoogle Scholar
  26. Inoue, Y., Shimojo, N., Suzuki, Y., Campos Alberto, E. J., Yamaide, A., Suzuki, S., Arima, T., Matsuura, T., Tomiita, M., Aoyagi, M., Hoshioka, A., Honda, A., Hata, A., and Kohno, Y. (2007). CD14 -550 C/T, which is related to the serum level of soluble CD14, is associated with the development of respiratory syncytial virus bronchiolitis in the Japanese population. J. Infect. Dis. 195, 1618–1624.PubMedCrossRefGoogle Scholar
  27. Janssen, R., Bont, L., Siezen, C. L., Hodemaekers, H. M., Ermers, M. J., Doornbos, G., van't, S. R., Wijmenga, C., Goeman, J. J., Kimpen, J. L., van Houwelingen, H. C., Kimman, T. G., and Hoebee, B. (2007). Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J. Infect. Dis. 196, 826–834.PubMedCrossRefGoogle Scholar
  28. Johnson, J. E., Gonzales, R. A., Olson, S. J., Wright, P. F., and Graham, B. S. (2007). The histopathology of fatal untreated human respiratory syncytial virus infection. Mod. Pathol. 20, 108–119.PubMedCrossRefGoogle Scholar
  29. Koenig, J. M., Stegner, J. J., Schmeck, A. C., Saxonhouse, M. A., and Kenigsberg, L. E. (2005). Neonatal neutrophils with prolonged survival exhibit enhanced inflammatory and cytotoxic responsiveness. Pediatr. Res. 57, 424–429.PubMedCrossRefGoogle Scholar
  30. Levy, O. (2005). Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonists. J. Endotoxin. Res. 11, 113–116.PubMedGoogle Scholar
  31. Levy, O. (2007). Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat. Rev. Immunol. 7, 379–390.PubMedCrossRefGoogle Scholar
  32. Levy, O., Coughlin, M., Cronstein, B. N., Roy, R. M., Desai, A., and Wessels, M. R. (2006). The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn. J. Immunol. 177, 1956–1966.PubMedGoogle Scholar
  33. Levy, O., Zarember, K. A., Roy, R. M., Cywes, C., Godowski, P. J., and Wessels, M. R. (2004). Selective impairment of TLR-mediated innate immunity in human newborns: neonatal blood plasma reduces monocyte TNF-alpha induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848. J. Immunol. 173, 4627–4634.PubMedGoogle Scholar
  34. Martinez, F. D., Morgan, W. J., Wright, A. L., Holberg, C. J., and Taussig, L. M. (1988). Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. N. Engl. J. Med. 319, 1112–1117.PubMedCrossRefGoogle Scholar
  35. Molloy, E. J., O'Neill, A. J., Grantham, J. J., Sheridan-Pereira, M., Fitzpatrick, J. M., Webb, D. W., and Watson, R. W. (2005). Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have differential effects on neonatal and adult neutrophil survival and function. Pediatr. Res. 57, 806–812.PubMedCrossRefGoogle Scholar
  36. Openshaw, P. J. M. (1995). Immunopathological mechanisms in respiratory syncytial virus disease. Springer Semin Immunopathol. 17, 187–201.PubMedCrossRefGoogle Scholar
  37. Peebles, R. S., Jr. and Graham, B. S. (2005). Pathogenesis of respiratory syncytial virus infection in the murine model. Proc. Am. Thorac. Soc. 2, 110–115.Google Scholar
  38. Puthothu, B., Forster, J., Heinzmann, A., and Krueger, M. (2006a). TLR-4 and CD14 polymorphisms in respiratory syncytial virus associated disease. Dis. Markers 22, 303–308.Google Scholar
  39. Puthothu, B., Krueger, M., Forster, J., and Heinzmann, A. (2006b). Association between severe respiratory syncytial virus infection and IL13/IL4 haplotypes. J. Infect. Dis. 193, 438–441.Google Scholar
  40. Renzi, P. M., Turgeon, J. P., Marcotte, J. E., Drblik, S. P., Berube, D., Gagnon, M. F., and Spier, S. (1999). Reduced interferon-gamma production in infants with bronchiolitis and asthma. Am. J. Respir. Crit Care Med. 159, 1417–1422.PubMedGoogle Scholar
  41. Rudd, B. D., Smit, J. J., Flavell, R. A., Alexopoulou, L., Schaller, M. A., Gruber, A., Berlin, A. A., and Lukacs, N. W. (2006). Deletion of TLR3 alters the pulmonary immune environment and mucus production during respiratory syncytial virus infection. J. Immunol. 176, 1937–1942.PubMedGoogle Scholar
  42. Schlender, J., Bossert, B., Buchholz, U., and Conzelmann, K. K. (2000). Bovine respiratory syncytial virus nonstructural proteins NS1 and NS2 cooperatively antagonize alpha/beta interferon-induced antiviral response. J. Virol. 74, 8234–8242.PubMedCrossRefGoogle Scholar
  43. Schlender, J., Hornung, V., Finke, S., Gunthner-Biller, M., Marozin, S., Brzozka, K., Moghim, S., Endres, S., Hartmann, G., and Conzelmann, K. K. (2005). 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. 79, 5507–5515.PubMedCrossRefGoogle Scholar
  44. Simoes, E. A. F. (1999). Respiratory syncytial virus infection. Lancet 354, 847–852.PubMedGoogle Scholar
  45. Smyth, R. L. and Openshaw, P. J. (2006). Bronchiolitis. Lancet 368, 312–322.PubMedCrossRefGoogle Scholar
  46. Stein, R. T., Sherill, D., Morgan, W. J., Holberg, C. J., Halonen, M., Taussig, L. M., Wright, A. L., and Martinez, F. D. (1999). Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13. Lancet 354, 541–545.PubMedCrossRefGoogle Scholar
  47. Tal, G., Mandelberg, A., Dalal, I., Cesar, K., Somekh, E., Tal, A., Oron, A., Itskovich, S., Ballin, A., Houri, S., Beigelman, A., Lider, O., Rechavi, G., and Amariglio, N. (2004). Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease. J. Infect. Dis. 189, 2057–2063.PubMedCrossRefGoogle Scholar
  48. The IMpact-RSV study group (1998). Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 102, 531–537.CrossRefGoogle Scholar
  49. van Woensel, J. and Kimpen, J. (2000). Therapy for respiratory tract infections caused by respiratory syncytial virus. Eur. J. Pediatr. 159, 391–398.PubMedCrossRefGoogle Scholar
  50. Wang, H., Peters, N., and Schwarze, J. (2006). Plasmacytoid dendritic cells limit viral replication, pulmonary inflammation, and airway hyperresponsiveness in respiratory syncytial virus infection. J. Immunol. 177, 6263–6270.PubMedGoogle Scholar
  51. Yusuf, S., Piedimonte, G., Auais, A., Demmler, G., Krishnan, S., VAN, C. P., Singleton, R., Broor, S., Parveen, S., Avendano, L., Parra, J., Chavez-Bueno, S., DE Sierra, T. M., Simoes, E. A., Shaha, S., and Welliver, R. (2007). The relationship of meteorological conditions to the epidemic activity of respiratory syncytial virus. Epidemiol. Infect. 135, 1077–1090.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department Pediatric Infectious DiseasesUniversity Medical Center Utrecht, Rm KE4.133.13508 AB Utrecht

Personalised recommendations