| Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction. | |
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MedLine Citation:
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PMID: 20479248 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Induction of type I interferons (IFN) is a central feature of innate immune responses to microbial pathogens and is mediated via Toll-like receptor (TLR)-dependent and -independent pathways. Prothymosin-alpha (ProTalpha), a small acidic protein produced and released by CD8(+) T cells, inhibits HIV-1, although the mechanism for its antiviral activity was not known. We demonstrate that exogenous ProTalpha acts as a ligand for TLR4 and stimulates type I IFN production to potently suppress HIV-1 after entry into cells. These activities are induced by native and recombinant ProTalpha, retained by an acidic peptide derived from ProTalpha, and lost in the absence of TLR4. Furthermore, we demonstrate that ProTalpha accounts for some of the soluble postintegration HIV-1 inhibitory activity long ascribed to CD8(+) cells. Thus, a protein produced by CD8(+) T cells of the adaptive immune system can exert potent viral suppressive activity through an innate immune response. Understanding the mechanism of IFN induction by ProTalpha may provide therapeutic leads for IFN-sensitive viruses. |
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Authors:
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Arevik Mosoian; Avelino Teixeira; Colin S Burns; Leif E Sander; G Luca Gusella; Cijiang He; J Magarian Blander; Paul Klotman; Mary E Klotman |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-17 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-10 Completed Date: 2010-06-29 Revised Date: 2010-09-30 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 10178-83 Citation Subset: IM |
Affiliation:
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Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. arevik.mosoian@mssm.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Vesicular Transport
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immunology Amino Acid Sequence Animals Anti-HIV Agents / immunology, pharmacology CD8-Positive T-Lymphocytes / immunology HIV-1 / drug effects*, genetics, immunology, physiology Humans Immunity, Innate / drug effects Interferon Type I / biosynthesis*, genetics Ligands Macrophages / drug effects, immunology, virology Mice Mice, Knockout Molecular Sequence Data Myeloid Differentiation Factor 88 / immunology Protein Precursors / genetics, immunology, pharmacology* RNA, Messenger / genetics, metabolism Recombinant Proteins / genetics, immunology, pharmacology Sequence Homology, Amino Acid Thymosin / analogs & derivatives*, genetics, immunology, pharmacology Toll-Like Receptor 4 / drug effects*, metabolism* Tumor Necrosis Factor-alpha / biosynthesis, genetics Virus Replication / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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AI76092-01A1/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Vesicular Transport; 0/Anti-HIV Agents; 0/Interferon Type I; 0/Ligands; 0/MYD88 protein, human; 0/Myeloid Differentiation Factor 88; 0/Protein Precursors; 0/RNA, Messenger; 0/Recombinant Proteins; 0/TICAM1 protein, human; 0/TLR4 protein, human; 0/Toll-Like Receptor 4; 0/Tumor Necrosis Factor-alpha; 0/prothymosin alpha; 61512-21-8/Thymosin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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