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Inducible nitric oxide contributes to viral pathogenesis following highly pathogenic influenza virus infection in

Lucy A Perrone1, Jessica A Belser, Debra A Wadford

  • 1Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

The Journal of Infectious Diseases
|February 20, 2013
PubMed

Insights

Nitric oxide (NO) exacerbates severe outcomes in highly pathogenic influenza virus infections. Inhibiting NO production in mice reduced disease severity and mortality from H5N1 and 1918 influenza viruses.

Area of Science:

  • Immunology
  • Virology
  • Pathology

Background:

  • Highly pathogenic influenza A viruses (HPAIVs), such as avian H5N1 and the 1918 pandemic strain, cause severe respiratory disease.
  • Influenza infection leads to pulmonary congestion and inflammation, involving reactive oxygen species and immune cells.
  • Nitric oxide (NO) is a key signaling molecule in inflammatory responses, but its role in HPAIV pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of nitric oxide (NO) in the pathogenesis of highly pathogenic influenza virus infections in a mouse model.
  • To determine if NO levels are elevated during H5N1 and 1918 influenza virus infections.
  • To assess the impact of NO inhibition on disease severity and mortality.

Main Methods:

  • Mice were infected with H5N1, 1918, or seasonal H1N1 influenza viruses.
  • Nitric oxide (NO) levels were measured in infected mice.
  • Inducible NO synthase knockout (NOS2(-/-)) mice and wild-type littermates were challenged with HPAIVs.
  • Mice infected with the 1918 virus were treated with a nitric oxide synthase (NOS) inhibitor.

Main Results:

  • Mice infected with H5N1 and 1918 viruses showed higher NO levels compared to those infected with seasonal H1N1.
  • NOS2(-/-) mice exhibited reduced morbidity, mortality, and lung cytokine production after H5N1 and 1918 virus challenge.
  • Treatment with a NOS inhibitor delayed weight loss and mortality in mice infected with the 1918 virus.

Conclusions:

  • Nitric oxide (NO) plays a significant role in the pathogenesis of H5N1 and 1918 influenza virus infections.
  • Inhibition of NO production or signaling can ameliorate disease severity and reduce mortality in HPAIV infections.
  • Targeting NO pathways may represent a therapeutic strategy for severe influenza.

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