1887

Abstract

Human metapneumovirus (hMPV) is a major cause of upper and lower respiratory-tract infection in infants, the elderly and immunocompromised individuals. Virus-directed cellular immunity elicited by hMPV infection is poorly understood, in contrast to the phylogenetically and clinically related pathogen human respiratory syncytial virus (hRSV). In a murine model of acute lower respiratory-tract infection with hMPV, we demonstrate the accumulation of gamma interferon (IFN-)-producing CD8 T cells in the airways and lungs at day 7 post-infection (p.i.), associated with cytotoxic T lymphocytes (CTLs) directed to an epitope of the M2-1 protein. This CTL immunity was accompanied by increased pulmonary expression of Th1 cytokines IFN- and interleukin (IL)-12 and antiviral cytokines (IFN-), as well as chemokines Mip-1, Mip-1, Mig, IP-10 and CX3CL1. There was also a moderate increase in Th2-type cytokines IL-4 and IL-10 compared with uninfected mice. At 21 days p.i., a strong CTL response could be recalled from the spleen. A similar pattern of CTL induction to the homologous M2-1 CTL epitope of hRSV, and of cytokine/chemokine induction, was observed following infection with hRSV, highlighting similarities in the cellular immune response to the two related pathogens.

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2010-05-01
2024-03-28
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References

  1. Alvarez, R. & Tripp, R. A.(2005). The immune response to human metapneumovirus is associated with aberrant immunity and impaired virus clearance in BALB/c mice. J Virol 79, 5971–5978.[CrossRef] [Google Scholar]
  2. Alvarez, R., Harrod, K. S., Shieh, W. J., Zaki, S. & Tripp, R. A.(2004). Human metapneumovirus persists in BALB/c mice despite the presence of neutralizing antibodies. J Virol 78, 14003–14011.[CrossRef] [Google Scholar]
  3. Barends, M., Boelen, A., de Rond, L., Kwakkel, J., Bestebroer, T., Dormans, J., Neijens, H. & Kimman, T.(2002). Influence of respiratory syncytial virus infection on cytokine and inflammatory responses in allergic mice. Clin Exp Allergy 32, 463–471.[CrossRef] [Google Scholar]
  4. Baumeister, E. G., Hunicken, D. S. & Savy, V. L.(2003). RSV molecular characterization and specific antibody response in young children with acute lower respiratory infection. J Clin Virol 27, 44–51.[CrossRef] [Google Scholar]
  5. Boivin, G., Abed, Y., Pelletier, G., Ruel, L., Moisan, D., Cote, S., Peret, T. C., Erdman, D. D. & Anderson, L. J.(2002). Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups. J Infect Dis 186, 1330–1334.[CrossRef] [Google Scholar]
  6. Bosis, S., Esposito, S., Niesters, H. G., Crovari, P., Osterhaus, A. D. & Principi, N.(2005). Impact of human metapneumovirus in childhood: comparison with respiratory syncytial virus and influenza viruses. J Med Virol 75, 101–104.[CrossRef] [Google Scholar]
  7. Braciale, T. J.(2005). Respiratory syncytial virus and T cells: interplay between the virus and the host adaptive immune system. Proc Am Thorac Soc 2, 141–146.[CrossRef] [Google Scholar]
  8. Darniot, M., Pitoiset, C., Petrella, T., Aho, S., Pothier, P. & Manoha, C.(2009). Age-associated aggravation of clinical disease after primary metapneumovirus infection of BALB/c mice. J Virol 83, 3323–3332.[CrossRef] [Google Scholar]
  9. Douville, R. N., Bastien, N., Li, Y., Pochard, P., Simons, F. E. S. & Hayglass, K. T.(2006). Human metapneumovirus elicits weak IFN-γ memory responses compared with respiratory syncytial virus. J Immunol 176, 5848–5855.[CrossRef] [Google Scholar]
  10. Ebihara, T., Endo, R., Kikuta, H., Ishiguro, N., Ishiko, H. & Kobayashi, K.(2004). Comparison of the seroprevalence of human metapneumovirus and human respiratory syncytial virus. J Med Virol 72, 304–306.[CrossRef] [Google Scholar]
  11. Esper, F., Boucher, D., Weibel, C., Martinello, R. A. & Kahn, J. S.(2003). Human metapneumovirus infection in the United States: clinical manifestations associated with a newly emerging respiratory infection in children. Pediatrics 111, 1407–1410.[CrossRef] [Google Scholar]
  12. Garcia-Garcia, M. L., Calvo, C., Casas, I., Bracamonte, T., Rellan, A., Gozalo, F., Tenorio, T. & Perez-Brena, P.(2007). Human metapneumovirus bronchiolitis in infancy is an important risk factor for asthma at age 5. Pediatr Pulmonol 42, 458–464.[CrossRef] [Google Scholar]
  13. Graham, B. S., Bunton, L. A., Wright, P. F. & Karzon, D. T.(1991). Role of T-lymphocyte subsets in the pathogenesis of primary infection and rechallenge with syncytial virus in mice. J Clin Invest 88, 1026–1033.[CrossRef] [Google Scholar]
  14. Guerrero-Plata, A., Casola, A. & Garofalo, R. P.(2005). Human metapneumovirus induces a profile of lung cytokines distinct from that of respiratory syncytial virus. J Virol 79, 14992–14997.[CrossRef] [Google Scholar]
  15. Hall, C. B., Powell, K. R., MacDonald, N. E., Gala, C. L., Menegus, M. E., Suffin, S. C. & Cohen, H. J.(1986). Respiratory syncytial viral infection in children with compromised immune function. N Engl J Med 315, 77–81.[CrossRef] [Google Scholar]
  16. Hamelin, M. E., Yim, K., Kuhn, K. H., Cragin, R. P., Boukhvalova, M., Blanco, J. C., Prince, G. A. & Boivin, G.(2005). Pathogenesis of human metapneumovirus lung infection in BALB/c mice and cotton rats. J Virol 79, 8894–8903.[CrossRef] [Google Scholar]
  17. Herd, K. A., Mahalingam, S., Mackay, I. M., Nissen, M., Sloots, T. P. & Tindle, R. W.(2006). Cytotoxic T-lymphocyte epitope vaccination protects against human metapneumovirus infection and disease in mice. J Virol 80, 2034–2044.[CrossRef] [Google Scholar]
  18. Herd, K. A., Nissen, M. D., Hopkins, P. M., Sloots, T. P. & Tindle, R. W.(2008). Major histocompatibility complex class I cytotoxic T lymphocyte immunity to human metapneumovirus (hMPV) in individuals with previous hMPV infection and respiratory disease. J Infect Dis 197, 584–592.[CrossRef] [Google Scholar]
  19. Hertz, M., Mahalingam, S., Dalum, I., Klysner, S., Mattes, J., Neisig, A., Mouritsen, S., Foster, P. S. & Gautam, A.(2001). Active vaccination against IL-5 bypasses immunological tolerance and ameliorates experimental asthma. J Immunol 167, 3792–3799.[CrossRef] [Google Scholar]
  20. Huck, B., Neumann-Haefelin, D., Schmitt-Graef, A., Weckmann, M., Mattes, J., Ehl, S. & Falcone, V.(2007). Human metapneumovirus induces more severe disease and stronger innate immune response in BALB/c mice as compared with respiratory syncytial virus. Respir Res 8, 6[CrossRef] [Google Scholar]
  21. Kolli, D., Bataki, E. L., Spetch, L., Guerrero-Plata, A., Jewell, A. M., Piedra, P. A., Milligan, G. N., Garofalo, R. P. & Casola, A.(2008). T lymphocytes contribute to antiviral immunity and pathogenesis in experimental human metapneumovirus infection. J Virol 82, 8560–8569.[CrossRef] [Google Scholar]
  22. Mao, H. W., Yang, X. Q. & Zhao, X. D.(2008). Characterization of human metapneumoviruses isolated in Chongqing, China. Chin Med J (Engl) 121, 2254–2257. [Google Scholar]
  23. Melendi, G. A., Zavala, F., Buchholz, U. J., Boivin, G., Collins, P. L., Kleeberger, S. R. & Polack, F. P.(2007). Mapping and characterization of the primary and anamnestic H-2d-restricted cytotoxic T-lymphocyte response in mice against human metapneumovirus. J Virol 81, 11461–11467.[CrossRef] [Google Scholar]
  24. Nissen, M. D., Siebert, D. J., Mackay, I. M., Sloots, T. P. & Withers, S. J.(2002). Evidence of human metapneumovirus in Australian children. Med J Aust 176, 188 [Google Scholar]
  25. Openshaw, P. J., Anderson, K., Wertz, G. W. & Askonas, B. A.(1990). The 22,000-kilodalton protein of respiratory syncytial virus is a major target for Kd -restricted cytotoxic T lymphocytes from mice primed by infection. J Virol 64, 1683–1689. [Google Scholar]
  26. Ostler, T., Schamel, K., Hussell, T., Openshaw, P., Hausmann, J. & Ehl, S.(2001). An improved protocol for measuring cytotoxic T cell activity in anatomic compartments with low cell numbers. J Immunol Methods 257, 155–161.[CrossRef] [Google Scholar]
  27. Peiris, J. S., Tang, W. H., Chan, K. H., Khong, P. L., Guan, Y., Lau, Y. L. & Chiu, S. S.(2003). Children with respiratory disease associated with metapneumovirus in Hong Kong. Emerg Infect Dis 9, 628–633.[CrossRef] [Google Scholar]
  28. Pierangeli, A., Gentile, M., Di Marco, P., Pagnotti, P., Scagnolari, C., Trombetti, S., Lo, R. L., Tromba, V., Moretti, C. & other authors(2007). Detection and typing by molecular techniques of respiratory viruses in children hospitalized for acute respiratory infection in Rome, Italy. J Med Virol 79, 463–468.[CrossRef] [Google Scholar]
  29. Ramshaw, I. A., Ramsay, A. J., Karupiah, G., Rolph, M. S., Mahalingam, S. & Ruby, J. C.(1997). Cytokines and immunity to viral infections. Immunol Rev 159, 119–135.[CrossRef] [Google Scholar]
  30. Rutigliano, J. A., Rock, M. T., Johnson, A. K., Crowe, J. E., Jr & Graham, B. S.(2005). Identification of an H-2D(b)-restricted CD8+ cytotoxic T lymphocyte epitope in the matrix protein of respiratory syncytial virus. Virology 337, 335–343.[CrossRef] [Google Scholar]
  31. Semple, M. G., Cowell, A., Dove, W., Greensill, J., McNamara, P. S., Halfhide, C., Shears, P., Smyth, R. L. & Hart, C. A.(2005). Dual infection of infants by human metapneumovirus and human respiratory syncytial virus is strongly associated with severe bronchiolitis. J Infect Dis 191, 382–386.[CrossRef] [Google Scholar]
  32. Stockton, J., Stephenson, I., Fleming, D. & Zambon, M.(2002). Human metapneumovirus as a cause of community-acquired respiratory illness. Emerg Infect Dis 8, 897–901.[CrossRef] [Google Scholar]
  33. Tauro, S., Su, Y. C., Thomas, S., Schwarze, J., Matthaei, K. I., Townsend, D., Simson, L., Tripp, R. A. & Mahalingam, S.(2008). Molecular and cellular mechanisms in the viral exacerbation of asthma. Microbes Infect 10, 1014–1023.[CrossRef] [Google Scholar]
  34. van den Hoogen, B. G., de Jong, J. C., Groen, J., Kuiken, T., de Groot, R., Fouchier, R. A. & Osterhaus, A. D.(2001). A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med 7, 719–724.[CrossRef] [Google Scholar]
  35. van den Hoogen, B. G., van Doornum, G. J., Fockens, J. C., Cornelissen, J. J., Beyer, W. E., de Groot, R., Osterhaus, A. D. & Fouchier, R. A.(2003). Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients. J Infect Dis 188, 1571–1577.[CrossRef] [Google Scholar]
  36. van den Hoogen, B. G., Osterhaus, D. M. & Fouchier, R. A.(2004). Clinical impact and diagnosis of human metapneumovirus infection. Pediatr Infect Dis J 23, S25–S32.[CrossRef] [Google Scholar]
  37. Ward, K. A., Lambden, P. R., Ogilvie, M. M. & Watt, P. J.(1983). Antibodies to respiratory syncytial virus polypeptides and their significance in human infection. J Gen Virol 64, 1867–1876.[CrossRef] [Google Scholar]
  38. Welliver, R. C., Sr(2008). The immune response to respiratory syncytial virus infection: friend or foe? Clin Rev Allergy Immunol 34, 163–173.[CrossRef] [Google Scholar]
  39. Williams, J. V., Crowe, J. E., Jr, Enriquez, R., Minton, P., Peebles, R. S., Jr, Hamilton, R. G., Higgins, S., Griffin, M. & Hartert, T. V.(2005). Human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults. J Infect Dis 192, 1149–1153.[CrossRef] [Google Scholar]
  40. Williams, J. V., Wang, C. K., Yang, C. F., Tollefson, S. J., House, F. S., Heck, J. M., Chu, M., Brown, J. B., Lintao, J. & other authors(2006). The role of human metapneumovirus in upper respiratory tract infections in children: a 20-year experience. J Infect Dis 193, 387–395.[CrossRef] [Google Scholar]
  41. Woo, W. P., Doan, T., Herd, K. A., Netter, H. J. & Tindle, R. W.(2006). Hepatitis B surface antigen vector delivers protective cytotoxic T-lymphocyte responses to disease-relevant foreign epitopes. J Virol 80, 3975–3984.[CrossRef] [Google Scholar]
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