tetano
Editor, Senior Moderator
J Innate Immun. 2015 May 5. [Epub ahead of print]
[h=1]A RIG-I 2CARD-MAVS200 Chimeric Protein Reconstitutes IFN-β Induction and Antiviral Response in Models Deficient in Type I IFN Response.[/h] Nistal-Vill?n E[SUP]1[/SUP], Rodr?guez-Garc?a E, Di Scala M, Ferrero-Laborda R, Olag?e C, Vales ?, Carte-Abad B, Crespo I, Garc?a-Sastre A, Prieto J, Larrea E, Gonz?lez-Aseguinolaza G.
[h=3]Author information[/h]
[h=3]Abstract[/h] 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. ? 2015 S. Karger AG, Basel.
PMID: 25966783 [PubMed - as supplied by publisher]
[h=1]A RIG-I 2CARD-MAVS200 Chimeric Protein Reconstitutes IFN-β Induction and Antiviral Response in Models Deficient in Type I IFN Response.[/h] Nistal-Vill?n E[SUP]1[/SUP], Rodr?guez-Garc?a E, Di Scala M, Ferrero-Laborda R, Olag?e C, Vales ?, Carte-Abad B, Crespo I, Garc?a-Sastre A, Prieto J, Larrea E, Gonz?lez-Aseguinolaza G.
[h=3]Author information[/h]
[h=3]Abstract[/h] 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. ? 2015 S. Karger AG, Basel.
PMID: 25966783 [PubMed - as supplied by publisher]