INHIBITION OF THE TYPE I INTERFERON ANTIVIRAL RESPONSE BY ZIKA VIRUS NS4B PROTEIN

SARRATEA MB; SANCHEZ ALBERTI ANDRES; AUGUSTO E. BIVONA; ANTONOGLOU MB; NOLI TRUANT S; FERNANDEZ LYNCH MJ; ROMASANTA PABLO; MARISA FERNDANDEZ; MALCHIODI E

Congreso; Congreso Sociedad Argentina de Inmunologia; 2017

Zika virus (ZIKV) illustrates the importance of flaviviruses as emerging vector-bornehuman pathogens. The major concern is the association between ZIKV infection andneurological disorders, such as congenital microcephaly and Guillain-Barré syndrome.According to the WHO, there are currently 54 countries with ongoing transmission of thevirus, including Argentina. Type I interferons (IFN I) play an important role in innate hostdefense against viruses. When a cell is infected with a virus, microbial components canbe sensed by intracellular receptors and promote IFN I production. However, recentstudies have shown that non-structural proteins of dengue virus and other flaviviruseshave developed ways to hinder this response. In the present work we aimed to studywhether one non-structural protein of ZIKV, NS4b, is able to inhibit IFN I response. Forthis purpose, we conducted transfection assays using RAW-Lucia ISG cells, an IFNreporter cell-line that secrete Lucia luciferase under ISRE promoter. Results showedthat cells transfected with plasmid encoding NS4b were able to inhibit luciferase signalsin a dose dependent manner compared to empty vectors (two-way ANOVA, p<0.05).This inhibition was also significant after treatment with TLR ligand, LPS, and STINGagonist, c-diAMP (two-way ANOVA+Tukey´s, p<0.05). Furthermore, NS4b(residues 25-127) was successfully cloned in the pet21a vector and produced in E. coliBL21(DE3)cells. The recombinant protein was used to obtain a specific antisera thatcould recognize NS4b in transfected cells. Although further analysis should be carriedout to elucidate the mechanism by which this protein is able to inhibit IFN I production,this results support the idea that flaviviruses are able to escape early host innateresponse. A better understanding of the flavivirus-host interactions during the differentevents of the viral life cycle may be essential not only for vaccine development but alsofor developing novel antiviral drugs.