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A RIG-I 2CARD-MAVS200 Chimeric Protein Reconstitutes IFN-? Induction and Antiviral Response in Models Deficient in Type I IFN Response.

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-? 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-? 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-? when compared to other stimulatory constructs. Furthermore, this human chimeric construct showed a superior ability to activate IFN-? expression in cells from various species. This construct was found to overcome the restrictions of blocking IFN-? 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-? induction and recover a partial antiviral state in different models that do not respond to recombinant IFN-? treatment.

SUBMITTER: Nistal-Villan E 

PROVIDER: S-EPMC4553127 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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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.

Nistal-Villán Estanislao E   Rodríguez-García Estefanía E   Di Scala Marianna M   Ferrero-Laborda Roberto R   Olagüe Cristina C   Vales África Á   Carte-Abad Beatriz B   Crespo Irene I   García-Sastre Adolfo A   Prieto Jesús J   Larrea Esther E   González-Aseguinolaza Gloria G  

Journal of innate immunity 20150505 5

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 a  ...[more]