Prothymosin-α inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction
| Autor: | Cijiang He, Colin S. Burns, Paul E. Klotman, J. Magarian Blander, Mary E. Klotman, G. Luca Gusella, Leif E. Sander, Arevik Mosoian, Avelino Teixeira |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Anti-HIV Agents
Molecular Sequence Data CD8-Positive T-Lymphocytes In Vitro Techniques Biology Ligands Virus Replication Prothymosin Alpha Mice Interferon medicine Animals Humans Amino Acid Sequence RNA Messenger Protein Precursors Mice Knockout Toll-like receptor Multidisciplinary Innate immune system Sequence Homology Amino Acid Tumor Necrosis Factor-alpha Macrophages Small acidic protein Biological Sciences Acquired immune system Molecular biology Immunity Innate Recombinant Proteins Cell biology Thymosin Toll-Like Receptor 4 Adaptor Proteins Vesicular Transport Interferon Type I Myeloid Differentiation Factor 88 HIV-1 TLR4 CD8 medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:10178-10183 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0914870107 |
| Popis: | 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-α (ProTα), 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 ProTα 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 ProTα, retained by an acidic peptide derived from ProTα, and lost in the absence of TLR4. Furthermore, we demonstrate that ProTα 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 ProTα may provide therapeutic leads for IFN-sensitive viruses. |
| Databáze: | OpenAIRE |
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