ZIKA VIRUS NS4B-C100S MUTANT PROTEIN WEAKLY BINDS TANK-BINDING KINASE AND ELICITS A STRONG ANTIVIRAL RESPONSE.

SARRATEA, MB; DANIELA REDOLFI; LAURA IANNANTUONO LOPEZ; SOFÍA NOLI TRUANT; GABRIELA ELENA GÓMEZ; JOSÉ MARIA DELFINO; ROY MARIUZZA; ANDRÉS SÁNCHEZ ALBERTI; MARISA MARIEL FERNÁNDEZ; EMILIO LUIS MALCHIODI

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ZIKA VIRUS NS4B-C100S MUTANT PROTEIN WEAKLY BINDS TANK-BINDING KINASE AND ELICITS A STRONG ANTIVIRAL RESPONSE Maria Belén Sarratea1, Daniela Redolfi1, Laura Iannantuono Lopez1, Sofía Noli Truant1, Gabriela Elena Gómez2, José Maria Delfino2, Roy Mariuzza3, Andrés Sánchez Alberti4, Marisa Mariel Fernández1, Emilio Luis Malchiodi1.1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Inmunología-IDEHU (UBA-CONICET), Buenos Aires, Argentina; 2Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Biológica-IQUIFIB (UBA-CONICET), Buenos Aires, Argentina; 3University of Maryland, Institute for Bioscience and Biotechnology Research (IBBR), Rockville, Maryland, USA; 4Universidad de Buenos Aires, Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología-IMPAM (UBA-CONICET), Buenos Aires, Argentina.Type I interferons (IFN-I) are key mediators in antiviral innate immunity. Nucleic acid sensing in the cytoplasm triggers TANK-binding kinase 1 (TBK1)- interferon regulatory factor 3 (IRF3) signaling axis and activate IFN-I transcription. Our previous reports demonstrated that the Zika virus (ZIKV) non-structural protein NS4B inhibits IFN-β production and directly binds TBK1. An attenuated ZIKV with NS4B C100S mutation showed a potent induction of antiviral immune response in a mouse model. In this work, we evaluated the effect of NS4B C100S in the antiviral cellular response and study how it affects the interaction with host ligands.For this purpose, we performed transfection assays with plasmids encoding recombinant ZIKV NS4B or NS4B-C100S mutant. We found that Hela cells transfected with NS4B-C100S secreted higher levels of IFN-β and IL-6 upon dsRNA analog stimulation (poly(I:C), compared to those transfected with wild type NS4B (ANOVA+Tukey´s, p