ZIKA VIRUS NS4b PROTEIN IMPAIRS TRANSLOCATION OF INTERFERON REGULATORY FACTOR 3 TO THE NUCLEUS

SARRATEA, MARÍA B.; ANTONOGLOU, MARÍA B.; NOLI TRUANT, SOFÍA; BIVONA, AUGUSTO; REDOLFI, DANIELA; IANNANTUONO, LAURA; TABOADA, GUILLERMO; SANCHEZ ALBERTI, ANDRÉS; FERNÁNDEZ, MARISA M.; MALCHIODI, EMILIO

CABA

Congreso; Reunión Conjunta de la Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Fisiología (SAFIS); 2018

Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Inmunología (SAI) y la Sociedad Argentina de Fisiología (SAFIS)

Type I interferons (IFN I) play an essential role in innate immunity against viralinfections. When a cell is infected with a virus, microbial components can be sensed byintracellular pattern recognition receptors, activating interferon regulatory factor 3 (IRF3)and inducing the production of IFN I. However, many pathogens have evolvedstrategies to evade immune sensing favoring their survival. Among them, flaviviral non-structural proteins, needed for viral replication, are involved in host immune evasion.Here, we aimed to broaden the understanding of the role of Zika virus (ZIKV) NS4bprotein in the inhibition of IFN I induction.For this purpose, we performed transfection assays with plasmid encoding recombinantZIKV NS4b. Using RAW-Lucia ISG cells, an IFN reporter cell-line, we showed that cellswith NS4b were able to reduce luciferase signals in a dose dependent mannercompared to empty vectors (two-way ANOVA, p<0.05). This reduction was maintainedafter treatment with TLR ligand, LPS, and STING agonist, c-diAMP (two-wayANOVA+Tukey´s, p<0.05). We also conducted immunoprecipitation assays, confirmingthat NS4b interacts with TANK-binding kinase1 (TBK1), as recently reported.Furthermore, by confocal microscopy we were able to identify that ZIKV NS4b aloneimpairs IRF3 translocation to the nucleus in Hela cells.ZIKV is still an international concern. At present, there is no approved vaccine ortreatment against ZIKV infection, hence a better understanding of molecular interactionsis needed. Our results add evidence that ZIKV NS4b can be involved in disruptingTBK1/IRF3 cascade. Because of this and the role of ZIKV NS4b in assembling thereplication complex, we believe that it may be a promising target for antiviral drugdevelopment.