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A RIG-I 2CARD-MAVS200 Chimeric Protein Reconstitutes IFN-β Induction and Antiviral Response in Models Deficient in Type I IFN Response.
- Source :
-
Journal of innate immunity [J Innate Immun] 2015; Vol. 7 (5), pp. 466-81. Date of Electronic Publication: 2015 May 05. - Publication Year :
- 2015
-
Abstract
- RIG-I-like receptors (RLRs) are cellular sensor proteins that detect certain RNA species produced during viral infections. RLRs activate a signaling cascade that results in the production of IFN-β as well as several other cytokines with antiviral and proinflammatory activities. We explored the potential of different constructs based on RLRs to induce the IFN-β pathway and create an antiviral state in type I IFN-unresponsive models. A chimeric construct composed of RIG-I 2CARD and the first 200 amino acids of MAVS (2CARD-MAVS200) showed an enhanced ability to induce IFN-β when compared to other stimulatory constructs. Furthermore, this human chimeric construct showed a superior ability to activate IFN-β expression in cells from various species. This construct was found to overcome the restrictions of blocking IFN-β induction or signaling by a number of viral IFN-antagonist proteins. Additionally, the antiviral activity of this chimera was demonstrated in influenza virus and HBV infection mouse models using adeno-associated virus (AAV) vectors as a delivery vehicle. We propose that AAV vectors expressing 2CARD-MAVS200 chimeric protein can reconstitute IFN-β induction and recover a partial antiviral state in different models that do not respond to recombinant IFN-β treatment.<br /> (© 2015 S. Karger AG, Basel.)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Animals
DEAD Box Protein 58
DEAD-box RNA Helicases genetics
Dependovirus genetics
Disease Models, Animal
Female
HEK293 Cells
Hepatitis B, Chronic immunology
Humans
Immunity, Innate
Interferon-beta genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Orthomyxoviridae Infections immunology
Peptide Fragments genetics
Receptors, Immunologic
Recombinant Fusion Proteins genetics
Signal Transduction genetics
Adaptor Proteins, Signal Transducing metabolism
DEAD-box RNA Helicases metabolism
Hepatitis B virus immunology
Hepatitis B, Chronic therapy
Influenza A virus immunology
Interferon-beta metabolism
Orthomyxoviridae Infections therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1662-8128
- Volume :
- 7
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of innate immunity
- Publication Type :
- Academic Journal
- Accession number :
- 25966783
- Full Text :
- https://doi.org/10.1159/000375262