| A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. | |
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MedLine Citation:
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PMID: 20829794 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dendritic cells serve a key function in host defence, linking innate detection of microbes to activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of human immunodeficiency virus (HIV) by host innate pattern-recognition receptors and subsequent coupling to antiviral T-cell responses is not yet known. Dendritic cells are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. Here we show that, when dendritic cell resistance to infection is circumvented, HIV-1 induces dendritic cell maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly synthesized HIV-1 capsid with cellular cyclophilin A (CYPA) and the subsequent activation of the transcription factor IRF3. Because the peptidylprolyl isomerase CYPA also interacts with HIV-1 capsid to promote infectivity, our results indicate that capsid conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell-intrinsic sensor for HIV-1 exists in dendritic cells and mediates an antiviral immune response, but it is not typically engaged owing to the absence of dendritic cell infection. The virulence of HIV-1 may be related to evasion of this response, the manipulation of which may be necessary to generate an effective HIV-1 vaccine. |
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Authors:
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Nicolas Manel; Brandon Hogstad; Yaming Wang; David E Levy; Derya Unutmaz; Dan R Littman |
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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 |
Journal Detail:
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Title: Nature Volume: 467 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-10 Completed Date: 2010-10-07 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
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Languages: eng Pagination: 214-7 Citation Subset: IM |
Affiliation:
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Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE22589 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Capsid Proteins
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immunology Cell Line Cyclophilin A / immunology Dendritic Cells / cytology, immunology*, metabolism, virology* HIV Infections / immunology*, virology HIV-1 / immunology*, physiology Humans Immunity, Innate* Interferon Regulatory Factor-3 / genetics, metabolism Lymphocyte Activation Monocytes / cytology T-Lymphocytes / immunology |
| Grant Support | |
ID/Acronym/Agency:
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AI28900/AI/NIAID NIH HHS; AI33856/AI/NIAID NIH HHS; R01 AI033856-16/AI/NIAID NIH HHS; R01AI065303/AI/NIAID NIH HHS; R21 AI084633-02/AI/NIAID NIH HHS; U54-AI057158/AI/NIAID NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Capsid Proteins; 0/Interferon Regulatory Factor-3; EC 5.2.1.-/Cyclophilin A |
| Comments/Corrections | |
Comment In:
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Nat Rev Immunol. 2010 Oct;10(10):678
[PMID:
20882684
]
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Erratum In:
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Nature. 2011 Feb 17;470(7334):424 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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