| p53 serves as a host antiviral factor that enhances innate and adaptive immune responses to influenza A virus. | |
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MedLine Citation:
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PMID: 22105999 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Several direct target genes of the p53 tumor suppressor have been identified within pathways involved in viral sensing, cytokine production, and inflammation, suggesting a potential role of p53 in antiviral immunity. The increasing need to identify immune factors to devise host-targeted therapies against pandemic influenza A virus (IAV) led us to investigate the role of endogenous wild-type p53 on the immune response to IAV. We observed that the absence of p53 resulted in delayed cytokine and antiviral gene responses in lung and bone marrow, decreased dendritic cell activation, and reduced IAV-specific CD8(+) T cell immunity. Consequently, p53(-/-) mice showed a more severe IAV-induced disease compared with their wild-type counterparts. These findings establish that p53 influences the antiviral response to IAV, affecting both innate and adaptive immunity. Thus, in addition to its established functions as a tumor suppressor gene, p53 serves as an IAV host antiviral factor that might be modulated to improve anti-IAV therapy and vaccines. |
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Authors:
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César Muñoz-Fontela; Michael Pazos; Igotz Delgado; William Murk; Sathish Kumar Mungamuri; Sam W Lee; Adolfo García-Sastre; Thomas M Moran; Stuart A Aaronson |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-11-21 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 187 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-14 Completed Date: 2012-02-07 Revised Date: 2012-02-08 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6428-36 Citation Subset: AIM; IM |
Affiliation:
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Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptive Immunity*
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genetics Animals CD8-Positive T-Lymphocytes / immunology, metabolism, pathology Dendritic Cells / immunology, metabolism, pathology Gene Expression Regulation, Viral / immunology* Immunity, Innate* / genetics Influenza A Virus, H1N1 Subtype / immunology* Influenza A Virus, H3N2 Subtype / immunology* Male Mice Mice, 129 Strain Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Orthomyxoviridae Infections / immunology*, metabolism, pathology Pneumonia, Viral / immunology, metabolism, pathology Tumor Suppressor Protein p53 / deficiency, genetics, physiology* Viral Regulatory and Accessory Proteins / deficiency, genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HHS266200700010C//PHS HHS; P01 CA80058-11/CA/NCI NIH HHS; R01 AI046954/AI/NIAID NIH HHS; R01 AI41111/AI/NIAID NIH HHS; U01 AI070469/AI/NIAID NIH HHS; U01 AI082970/AI/NIAID NIH HHS; U19 AI083025/AI/NIAID NIH HHS; U54 AI057158/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Tumor Suppressor Protein p53; 0/Viral Regulatory and Accessory Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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