Archives of Virology

, Volume 155, Issue 6, pp 905–914

Extrapulmonary tissue responses in cynomolgus macaques (Macaca fascicularis) infected with highly pathogenic avian influenza A (H5N1) virus

  • A.-E. Tolnay
  • C. R. Baskin
  • T. M. Tumpey
  • P. J. Sabourin
  • C. L. Sabourin
  • J. P. Long
  • J. A. Pyles
  • R. A. Albrecht
  • A. García-Sastre
  • M. G. Katze
  • H. Bielefeldt-Ohmann
Original Article


The mechanisms responsible for virulence of influenza viruses in humans remain poorly understood. A prevailing hypothesis is that the highly pathogenic virus isolates cause a severe cytokinemia precipitating acute respiratory distress syndrome and multiple organ dysfunction syndrome. Cynomolgus macaques (Macaca fascicularis) infected with a human highly pathogenic avian influenza (HPAI) H5N1 virus isolate (A/Vietnam/1203/2004) or reassortants of human influenza virus A/Texas/36/91 (H1N1) containing genes from the 1918 pandemic influenza A (H1N1) virus developed severe pneumonia within 24 h postinfection. However, virus spread beyond the lungs was only detected in the H5N1 group, and signs of extrapulmonary tissue reactions, including microglia activation and sustained up-regulation of inflammatory markers, most notably hypoxia inducible factor-1α (HIF-1α), were largely limited to this group. Extrapulmonary pathology may thus contribute to the morbidities induced by H5N1 viruses.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • A.-E. Tolnay
    • 1
    • 12
  • C. R. Baskin
    • 2
    • 3
    • 4
    • 13
  • T. M. Tumpey
    • 5
  • P. J. Sabourin
    • 6
  • C. L. Sabourin
    • 6
  • J. P. Long
    • 6
  • J. A. Pyles
    • 6
    • 14
  • R. A. Albrecht
    • 7
  • A. García-Sastre
    • 7
    • 8
    • 9
  • M. G. Katze
    • 2
    • 10
  • H. Bielefeldt-Ohmann
    • 1
    • 11
  1. 1.Department of Microbiology, Immunology and PathologyColorado State UniversityFort CollinsUSA
  2. 2.Washington National Primate Research CenterUniversity of WashingtonSeattleUSA
  3. 3.Department of Comparative MedicineUniversity of WashingtonSeattleUSA
  4. 4.Center for Infectious Diseases and Vaccinology, Biodesign InstituteArizona State UniversityTempeUSA
  5. 5.Influenza DivisionCenters for Disease Control and PreventionAtlantaUSA
  6. 6.Battelle Biomedical Research CenterWest JeffersonUSA
  7. 7.Department of MicrobiologyMount Sinai School of MedicineNew YorkUSA
  8. 8.Department of Medicine, Division of Infectious DiseasesMount Sinai School of MedicineNew YorkUSA
  9. 9.Global Health and Emerging Pathogens InstituteMount Sinai School of MedicineNew YorkUSA
  10. 10.Department of MicrobiologyUniversity of WashingtonSeattleUSA
  11. 11.School of Veterinary ScienceUniversity of QueenslandQldAustralia
  12. 12.Department of Biomedical SciencesColorado State UniversityFort CollinsUSA
  13. 13.Science Foundation ArizonaPhoenixUSA
  14. 14.Lovelace Respiratory Research InstituteAlbuquerqueUSA

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