| Replication-independent activation of human plasmacytoid dendritic cells by the paramyxovirus SV5 Requires TLR7 and autophagy pathways. | |
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MedLine Citation:
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PMID: 20605567 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The paramyxovirus Simian Virus 5 (SV5) is a poor inducer of interferon (IFN) secretion in all cell types tested so far, including primary epithelial cells and primary human myeloid dendritic cells. SV5 is hypothesized to limit induction of antiviral responses through control of viral gene expression and production of the V protein antagonist. Plasmacytoid dendritic cells (pDCs) are known to uniquely express toll-like receptor (TLR)-7 and are a main producer of IFN-alpha among peripheral blood mononuclear cells in response to many viruses. Here, we tested whether SV5 would remain a poor inducer of IFN in primary human pDCs. The efficiency of SV5 infection of pDCs could be increased by an increasing multiplicity of infection. pDCs infected by both live and UV-inactivated SV5 induced large amounts of IFN-alpha secretion and resulted in upregulation of maturation markers CD80 and CD86. However, IL-6 secretion was not induced by SV5 infection. When TLR7 signaling was inhibited, SV5 induced less IFN secretion and CD80 expression, and there was a corresponding increase in number of infected cells. Similar effects were seen with inhibitors of cellular autophagy pathways, suggesting that the SV5 activation of pDC requires access to the cytoplasm and autophagic sampling of cytoplasmic contents. These results have implications for control of SV5 infections in vivo and for development of SV5 as a vaccine vector. |
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Authors:
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Mary J Manuse; Caitlin M Briggs; Griffith D Parks |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-07-06 |
Journal Detail:
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Title: Virology Volume: 405 ISSN: 1096-0341 ISO Abbreviation: Virology Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-17 Completed Date: 2010-09-14 Revised Date: 2012-04-27 |
Medline Journal Info:
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Nlm Unique ID: 0110674 Medline TA: Virology Country: United States |
Other Details:
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Languages: eng Pagination: 383-9 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Microbiology and Immunology, School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1064, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD80 / metabolism Antigens, CD86 / metabolism Autophagy* Cells, Cultured Dendritic Cells / immunology*, virology Humans Interferon-alpha / immunology, metabolism* Simian virus 5 / immunology, pathogenicity*, radiation effects Toll-Like Receptor 7 / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AI060642/AI/NIAID NIH HHS; AI42023/AI/NIAID NIH HHS; DC009619/DC/NIDCD NIH HHS; R21 DC009619-02/DC/NIDCD NIH HHS; T32-AI007401/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD80; 0/Antigens, CD86; 0/Interferon-alpha; 0/TLR7 protein, human; 0/Toll-Like Receptor 7 |
| Comments/Corrections | |
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