Ion-Current-Based Temporal Proteomic Profiling of Influenza-A-Virus-Infected Mouse Lungs Revealed Underlying Mechanisms of Altered Integrity of the Lung Microvascular Barrier

Shichen Shen, Jun Li, Shannon Hilchey, Xiaomeng Shen, Chengjian Tu, Xing Qiu, Andrew Ng, Sina Ghaemmaghami, Hulin Wu, Martin S. Zand, Jun Qu

Research output: Contribution to journalArticle

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Abstract

Investigation of influenza-A-virus (IAV)-infected lung proteomes will greatly promote our understanding on the virus-host crosstalk. Using a detergent-cocktail extraction and digestion procedure and a reproducible ion-current-based method, we performed the first comprehensive temporal analysis of mouse IAV infection. Mouse lung tissues at three time points post-inoculation were compared with controls (n = 4/group), and >1600 proteins were quantified without missing value in any animal. Significantly changed proteins were identified at 4 days (n = 144), 7 days (n = 695), and 10 days (n = 396) after infection, with low false altered protein rates (1.73-8.39%). Functional annotation revealed several key biological processes involved in the systemic host responses. Intriguingly, decreased levels of several cell junction proteins as well as increased levels of tissue metalloproteinase MMP9 were observed, reflecting the IAV-induced structural breakdown of lung epithelial barrier. Supporting evidence of MMP9 activation came from immunoassays examining the abundance and phosphorylation states of all MAPKs and several relevant molecules. Importantly, IAV-induced MMP gelatinase expression was suggested to be specific to MMP9, and p38 MAPK may contribute predominantly to MMP9 elevation. These findings help to resolve the long-lasting debate regarding the signaling pathways of IAV-induced MMP9 expression and shed light on the molecular mechanisms underlying pulmonary capillary-alveolar leak syndrome that can occur during influenza infection.

LanguageEnglish
Pages540-553
Number of pages14
JournalJournal of Proteome Research
Volume15
Issue number2
DOIs
StatePublished - Feb 5 2016

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Influenza A virus
Viruses
Proteomics
Ions
Lung
Proteins
Capillary Leak Syndrome
Biological Phenomena
Gelatinases
Intercellular Junctions
Tissue
Matrix Metalloproteinase 9
p38 Mitogen-Activated Protein Kinases
Virus Diseases
Proteome
Infection
Phosphorylation
Matrix Metalloproteinases
Immunoassay
Detergents

Keywords

  • bottom-up proteomics
  • host factors
  • influenza
  • ion-current-based quantification
  • microvascular barrier

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry

Cite this

Ion-Current-Based Temporal Proteomic Profiling of Influenza-A-Virus-Infected Mouse Lungs Revealed Underlying Mechanisms of Altered Integrity of the Lung Microvascular Barrier. / Shen, Shichen; Li, Jun; Hilchey, Shannon; Shen, Xiaomeng; Tu, Chengjian; Qiu, Xing; Ng, Andrew; Ghaemmaghami, Sina; Wu, Hulin; Zand, Martin S.; Qu, Jun.

In: Journal of Proteome Research, Vol. 15, No. 2, 05.02.2016, p. 540-553.

Research output: Contribution to journalArticle

Shen, Shichen ; Li, Jun ; Hilchey, Shannon ; Shen, Xiaomeng ; Tu, Chengjian ; Qiu, Xing ; Ng, Andrew ; Ghaemmaghami, Sina ; Wu, Hulin ; Zand, Martin S. ; Qu, Jun. / Ion-Current-Based Temporal Proteomic Profiling of Influenza-A-Virus-Infected Mouse Lungs Revealed Underlying Mechanisms of Altered Integrity of the Lung Microvascular Barrier. In: Journal of Proteome Research. 2016 ; Vol. 15, No. 2. pp. 540-553.
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