Pathogenicity of pandemic H1N1 influenza A virus in immunocompromised cynomolgus macaques

PLoS One. 2013 Sep 23;8(9):e75910. doi: 10.1371/journal.pone.0075910. eCollection 2013.

Abstract

Pandemic (H1N1) 2009 influenza virus spread throughout the world since most people did not have immunity against the virus. In the post pandemic phase when many humans might possess immunity against the pandemic virus, one of the concerns is infection in immunocompromised people. Therefore, we used an immunosuppressed macaque model to examine pathogenicity of the pandemic (H1N1) 2009 virus under an immunocompromised condition. The virus in nasal samples of immunosuppressed macaques infected with the pandemic (H1N1) 2009 virus was detected longer after infection than was the virus in nasal samples of immunocompetent macaques. As expected, not only virus amounts but also virus propagation sites in the immunosuppressed macaques were larger than those in lungs of the immunocompetent macaques when they were infected with the pandemic virus. Immunosuppressed macaques possessed low levels of immune cells producing cytokines and chemokines, but levels of inflammatory cytokines/chemokine interleukin (IL)-6, IL-18, and monocyte chemotactic protein (MCP)-1 in lungs of the immunosuppressed macaques were higher than those in lungs of the immunocompetent macaques, though the differences were not statistically significant. Therefore, under an immunosuppressive condition, the pandemic influenza (H1N1) 2009 virus might cause more severe morbidity with high cytokine/chemokine production by the host innate immune system than that seen in macaques under the immunocompetent condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclophosphamide / pharmacology
  • Cyclosporine / pharmacology
  • Cytokines / immunology
  • Immunocompromised Host / immunology*
  • Immunohistochemistry
  • Immunosuppression Therapy / methods
  • Influenza A Virus, H1N1 Subtype / pathogenicity*
  • Lung / immunology
  • Macaca fascicularis
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / virology*
  • Virus Replication / physiology

Substances

  • Cytokines
  • Cyclosporine
  • Cyclophosphamide

Grants and funding

This work was supported by Regional Research and Development Resources Utilization Program, Japan Science and Technology Agency, the Grant from the Ministry of Education, Culture, Sports, Science and Technology, Japan, for Joint Research Program of the Research Center for Zoonosis Control, Hokkaido University and the Japan Initiative for Global Research Network on Infectious Diseases, and Grant-in-Aid for Scientific Research (B) JSPS KAKENHI Grant number 22390076. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.