1887

Abstract

Highly pathogenic H5N1 avian influenza viruses have caused infection in humans, with a high mortality rate, since 1997. While the pathogenesis of this infection is not completely understood, hypercytokinaemia and alveolar macrophages are thought to play a role. To gain further insight into the cytokine-mediated pathogenesis of this infection in humans, we measured various cytokines produced by primary human macrophages infected with H5N1, pandemic H1N1 or seasonal influenza viruses. We found that many cytokines were produced at higher levels on infection with the H5N1 strains tested compared with seasonal influenza viruses. Interestingly, the extent of cytokine induction varied among the H5N1 strains and did not correlate with replicative ability in macrophages. Further, a pandemic H1N1 virus induced higher levels of several cytokines compared with seasonal viruses and some H5N1 strains. Our results demonstrate that high cytokine induction is not a universal feature of all H5N1 viruses.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.030346-0
2011-06-01
2019-10-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/6/1428.html?itemId=/content/journal/jgv/10.1099/vir.0.030346-0&mimeType=html&fmt=ahah

References

  1. Abdel-Ghafar A. N. , Chotpitayasunondh T. , Gao Z. , Hayden F. G. , Nguyen D. H. , de Jong M. D. , Naghdaliyev A. , Peiris J. S. , Shindo N. et al. ( 2008; ). Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus. Update on avian influenza A (H5N1) virus infection in humans. . N Engl J Med 358:, 261–273. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bozza F. A. , Salluh J. I. , Japiassu A. M. , Soares M. , Assis E. F. , Gomes R. N. , Bozza M. T. , Castro-Faria-Neto H. C. , Bozza P. T. . ( 2007; ). Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. . Crit Care 11:, R49. [CrossRef] [PubMed]
    [Google Scholar]
  3. Cheung C. Y. , Poon L. L. , Lau A. S. , Luk W. , Lau Y. L. , Shortridge K. F. , Gordon S. , Guan Y. , Peiris J. S. . ( 2002; ). Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?. Lancet 360:, 1831–1837. [CrossRef] [PubMed]
    [Google Scholar]
  4. Claas E. C. , Osterhaus A. D. , van Beek R. , De Jong J. C. , Rimmelzwaan G. F. , Senne D. A. , Krauss S. , Shortridge K. F. , Webster R. G. . ( 1998; ). Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. . Lancet 351:, 472–477. [CrossRef] [PubMed]
    [Google Scholar]
  5. Dawood F. S. , Jain S. , Finelli L. , Shaw M. W. , Lindstrom S. , Garten R. J. , Gubareva L. V. , Xu X. , Bridges C. B. et al. ( 2009; ). Novel swine-origin influenza A (H1N1) virus investigation team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. . N Engl J Med 360:, 2605–2615. [CrossRef] [PubMed]
    [Google Scholar]
  6. de Jong M. D. , Bach V. C. , Phan T. Q. , Vo M. H. , Tran T. T. , Nguyen B. H. , Beld M. , Le T. P. , Truong H. K. et al. ( 2005; ). Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. . N Engl J Med 352:, 686–691. [CrossRef] [PubMed]
    [Google Scholar]
  7. de Jong M. D. , Simmons C. P. , Thanh T. T. , Hien V. M. , Smith G. J. , Chau T. N. , Hoang D. M. , Chau N. V. , Khanh T. H. et al. ( 2006; ). Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. . Nat Med 12:, 1203–1207. [CrossRef] [PubMed]
    [Google Scholar]
  8. Guan Y. , Poon L. L. , Cheung C. Y. , Ellis T. M. , Lim W. , Lipatov A. S. , Chan K. H. , Sturm-Ramirez K. M. , Cheung C. L. et al. ( 2004; ). H5N1 influenza: a protean pandemic threat. . Proc Natl Acad Sci U S A 101:, 8156–8161. [CrossRef] [PubMed]
    [Google Scholar]
  9. Kellum J. A. , Kong L. , Fink M. P. , Weissfeld L. A. , Yealy D. M. , Pinsky M. R. , Fine J. , Krichevsky A. , Delude R. L. , Angus D. C. . GenIMS Investigators ( 2007; ). Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. . Arch Intern Med 167:, 1655–1663. [CrossRef] [PubMed]
    [Google Scholar]
  10. Khan K. , Arino J. , Hu W. , Raposo P. , Sears J. , Calderon F. , Heidebrecht C. , Macdonald M. , Liauw J. et al. ( 2009; ). Spread of a novel influenza A (H1N1) virus via global airline transportation. . N Engl J Med 361:, 212–214. [CrossRef] [PubMed]
    [Google Scholar]
  11. Le Q. M. , Ito M. , Muramoto Y. , Hoang P. V. , Vuong C. D. , Sakai-Tagawa Y. , Kiso M. , Ozawa M. , Takano R. , Kawaoka Y. . ( 2010; ). Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam. . J Gen Virol 91:, 2485–2490. [CrossRef] [PubMed]
    [Google Scholar]
  12. Lee S. M. , Gardy J. L. , Cheung C. Y. , Cheung T. K. , Hui K. P. , Ip N. Y. , Guan Y. , Hancock R. E. , Peiris J. S. . ( 2009; ). Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages. . PLoS ONE 4:, e8072. [CrossRef] [PubMed]
    [Google Scholar]
  13. Logrippo G. A. , Hartman F. W. . ( 1955; ). Antigenicity of beta-propiolactone-inactivated virus vaccines. . J Immunol 75:, 123–128.[PubMed]
    [Google Scholar]
  14. Louie J. K. , Acosta M. , Winter K. , Jean C. , Gavali S. , Schechter R. , Vugia D. , Harriman K. , Matyas B. et al. ( 2009; ). Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. . JAMA 302:, 1896–1902. [CrossRef] [PubMed]
    [Google Scholar]
  15. Mok K. P. , Wong C. H. , Cheung C. Y. , Chan M. C. , Lee S. M. , Nicholls J. M. , Guan Y. , Peiris J. S. . ( 2009; ). Viral genetic determinants of H5N1 influenza viruses that contribute to cytokine dysregulation. . J Infect Dis 200:, 1104–1112. [CrossRef] [PubMed]
    [Google Scholar]
  16. Osterlund P. , Pirhonen J. , Ikonen N. , Rönkkö E. , Strengell M. , Mäkelä S. M. , Broman M. , Hamming O. J. , Hartmann R. et al. ( 2010; ). Pandemic H1N1 2009 influenza A virus induces weak cytokine responses in human macrophages and dendritic cells and is highly sensitive to the antiviral actions of interferons. . J Virol 84:, 1414–1422. [CrossRef] [PubMed]
    [Google Scholar]
  17. Peiris J. S. , Yu W. C. , Leung C. W. , Cheung C. Y. , Ng W. F. , Nicholls J. M. , Ng T. K. , Chan K. H. , Lai S. T. et al. ( 2004; ). Re-emergence of fatal human influenza A subtype H5N1 disease. . Lancet 363:, 617–619. [CrossRef] [PubMed]
    [Google Scholar]
  18. Peng Z. , Zhang Z. , Xu Y. . ( 1999; ). [Effect of Angelica sinensis injection on CD11c and CD14 expression in alveolar macrophage membrane of chronic bronchitis patients]. . Zhongguo Zhong Xi Yi Jie He Za Zhi 19:, 282–285 ( in Chinese).[PubMed]
    [Google Scholar]
  19. Shimizu T. , Fujimori F. , Shimaoka Y. , Narita J. , Takada T. , Tajima S. , Moriyama H. , Terada M. , Suzuki E. , Gejyo F. . ( 2007; ). Isolation and immunophenotyping of mononuclear cells from human lung tissue. . Intern Med 46:, 163–169. [CrossRef] [PubMed]
    [Google Scholar]
  20. Smith H. H. , Srb A. M. . ( 1951; ). Induction of mutations with beta-propiolactone. . Science 114:, 490–492. [CrossRef] [PubMed]
    [Google Scholar]
  21. Taylor P. R. , Martinez-Pomares L. , Stacey M. , Lin H. H. , Brown G. D. , Gordon S. . ( 2005; ). Macrophage receptors and immune recognition. . Annu Rev Immunol 23:, 901–944. [CrossRef] [PubMed]
    [Google Scholar]
  22. To K. F. , Chan P. K. , Chan K. F. , Lee W. K. , Lam W. Y. , Wong K. F. , Tang N. L. , Tsang D. N. , Sung R. Y. et al. ( 2001; ). Pathology of fatal human infection associated with avian influenza A H5N1 virus. . J Med Virol 63:, 242–246. [CrossRef] [PubMed]
    [Google Scholar]
  23. Uiprasertkul M. , Puthavathana P. , Sangsiriwut K. , Pooruk P. , Srisook K. , Peiris M. , Nicholls J. M. , Chokephaibulkit K. , Vanprapar N. , Auewarakul P. . ( 2005; ). Influenza A H5N1 replication sites in humans. . Emerg Infect Dis 11:, 1036–1041.[PubMed] [CrossRef]
    [Google Scholar]
  24. Woo P. C. , Tung E. T. , Chan K. H. , Lau C. C. , Lau S. K. , Yuen K. Y. . ( 2010; ). Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies. . J Infect Dis 201:, 346–353. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.030346-0
Loading
/content/journal/jgv/10.1099/vir.0.030346-0
Loading

Data & Media loading...

Supplements

vol. , part 6, pp. 1428 - 1434

Relative cytokine production by human macrophages from five different donors. [PDF](183 KB)



PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error