Influenza A virus induction of oxidative stress and MMP-9 is associated with severe lung pathology in a mouse model

Yu Hsiang Lee, Chai Lin Lai, Shih Hung Hsieh, Chi Chang Shieh, Li Min Huang, Betty A. Wu-Hsieh

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Infection by different strains of influenza virus presents different pictures. Whether the pathogenicity of influenza virus is defined by the ability of the virus to induce differential immunopathlogical responses in the lungs still remains unclear. We compared the immunopathological response induced by influenza virus A/WSN/33 (H1N1) and that by A/Panama-like (H3N2) virus in C57BL/6 mice. WSN virus, in contrast to Panama-like virus, induced high mortality and severe lung pathology accompanied by massive Gr-1+ and CD11b+ cell infiltration and high levels of CXCL6/GCP-2, CCL2/MCP-1 and TIMP-1 production. Infection by WSN virus but not by Panama-like virus induced up-regulation of the active and latent forms of MMP-9 in the lungs and MMP-2/9 inhibitor partially reduced WSN virus-induced lung pathology. Both Gr-1+ and CD11b+ cells in WSN virus-infected lungs produced reactive oxygen and nitrogen species (ROS/RNS). While wild type mice infected by WSN virus had severe lung pathology and the presence of oxidized phospholipids and numerous MMP-9+ cells in the lungs, ncf1 deficiency ablated their expression and manifested less lung pathology. Employing a pulmonary mouse model we demonstrated in this study that infection by virulent influenza virus is characterized by a heavy cellular infiltration, severe lung pathology which is accompanied by oxidative stress and MMP-9 production.

Original languageEnglish
Pages (from-to)411-422
Number of pages12
JournalVirus Research
Issue number2
Publication statusPublished - 2013 Dec 26

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Virology
  • Infectious Diseases

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