tetano
Editor, Senior Moderator
J Proteome Res. 2015 Dec 9. [Epub ahead of print]
[h=1]An Ion-Current-Based Temporal Proteomic Profiling of Influenza A Virus Infected Mouse Lungs Revealed Underlying Mechanisms of Altered Integrity of the Lung Microvascular Barrier.[/h] Shen S, Li J, Hilchey S, Shen X, Tu C, Qiu X, Ng A, Ghaemmaghami S, Wu H, ZAnd M, Qu J.
[h=3]Abstract[/h] 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 >1,600 proteins were quantified without missing value in any animal. Significantly changed proteins were identified at 4d(n=144), 7d(n=695) and 10d(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 for 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.
PMID: 26650791 [PubMed - as supplied by publisher]
[h=1]An Ion-Current-Based Temporal Proteomic Profiling of Influenza A Virus Infected Mouse Lungs Revealed Underlying Mechanisms of Altered Integrity of the Lung Microvascular Barrier.[/h] Shen S, Li J, Hilchey S, Shen X, Tu C, Qiu X, Ng A, Ghaemmaghami S, Wu H, ZAnd M, Qu J.
[h=3]Abstract[/h] 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 >1,600 proteins were quantified without missing value in any animal. Significantly changed proteins were identified at 4d(n=144), 7d(n=695) and 10d(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 for 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.
PMID: 26650791 [PubMed - as supplied by publisher]