ZIKA VIRUS NS4B PROTEIN TARGETS TANK-BINDING KINASE 1 TO INHIBIT TYPE I INTERFERON PRODUCTION

SARRATEA, MARÍA BELÉN; REDOLFI, DANIELA MARÍA; AMERIO CONSTANZA; IANNANTUONO LÓPEZ, LAURA VALERIA; NOLI TRUANT, SOFIA; SANCHEZ ALBERTI, ANDRÉS; MARIUZZA, ROY; FERNÁNDEZ, MARISA MARIEL; MALCHIODI, EMILIO

Virtual

Congreso; Reunión Anual de Sociedades de Biociencias; 2021

TypeI interferons (IFN I) play an essential role in antiviral innate immunity. Duringviral infections, cytosolic nucleic acids can be sensed by intracellularpattern recognition receptors, triggering TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 (IRF3) signaling axis to initiate IFN I transcription.However, many flavivirus use non-structural proteins to evade immune sensingfavoring their survival. Here, we aimed to study therole of Zika virus (ZIKV) NS4b protein in the inhibition of IFN I induction andits interaction with host ligands. For this purpose, we performed transfectionassays witha plasmid encoding recombinant ZIKV NS4b or ZIKV NS4b C100Smutant. UsingRAW-Lucia ISG cells, an IFN reporter cell-line, we showed that cells with ZIKVNS4b were able to reduce luciferase signals compared to empty vector. Interestingly,this reduction was abrogated with ZIKV NS4b C100S mutant (ANOVA+Tukey´s, p