| Double-stranded RNA-activated protein kinase regulates early innate immune responses during respiratory syncytial virus infection. | |
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MedLine Citation:
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PMID: 20038207 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Respiratory syncytial virus (RSV) is the most common cause of childhood viral bronchiolitis and lung injury. Inflammatory responses significantly contribute to lung pathologies during RSV infections and bronchiolitis but the exact mechanisms have not been completely defined. The double-stranded RNA-activated protein kinase (PKR) functions to inhibit viral replication and participates in several signaling pathways associated with innate inflammatory immune responses. Using a functionally defective PKR (PKR(-/-)) mouse model, we investigated the role of this kinase in early events of RSV-induced inflammation. Our data showed that bronchoalveolar lavage (BAL) fluid from infected PKR(-/-) mice had significantly lower levels of several innate inflammatory cytokines and chemokines. Histological examinations revealed that there was less lung injury in infected PKR(-/-) mice as compared to the wild type. A genome-wide analysis showed that several early antiviral and immune regulatory genes were affected by PKR activation. These data suggest that PKR is a signaling molecule for immune responses during RSV infections. |
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Authors:
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Radiah A Corn Minor; Gino V Limmon; Laura Miller-DeGraff; Darlene Dixon; Danica M K Andrews; Randal J Kaufman; Farhad Imani |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural |
Journal Detail:
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Title: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research Volume: 30 ISSN: 1557-7465 ISO Abbreviation: J. Interferon Cytokine Res. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-09 Completed Date: 2010-09-09 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 9507088 Medline TA: J Interferon Cytokine Res Country: United States |
Other Details:
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Languages: eng Pagination: 263-72 Citation Subset: IM |
Affiliation:
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North Carolina A&T University, Greensboro, North Carolina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chemokines / metabolism Enzyme Activation Gene Expression Profiling Gene Expression Regulation Genome / genetics Immunity, Innate / genetics, immunology* Lung / enzymology, pathology, virology Male Mice Mitogen-Activated Protein Kinases / metabolism Respiratory Syncytial Virus Infections / enzymology*, immunology* Respiratory Syncytial Viruses / immunology*, physiology Signal Transduction Viral Load / immunology Virus Replication eIF-2 Kinase / deficiency, genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK088227-02/DK/NIDDK NIH HHS; R37 DK042394-13/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokines; EC 2.7.11.1/eIF-2 Kinase; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
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