Zika virus (ZIKV) is a mosquito-borne virus belonging to the Flaviviridae family. It is an enveloped virus with a 10.8 kb long single-stranded positive-sense RNA genome, which encodes for 4 structural proteins and 7 non-structural proteins. ZIKV infections have been associated with severe complications , such as Guillain- Barré syndrome and microcephaly. This lead to a global health concern, and ZIKV was declared by WHO a public health emergency. Recent studies have shown ZIKV to interfere with human innate immune responses by inhibiting the expression of IFN-induced genes. At present it is not known whether ZIKV can also interfere with the RIG-I or TLR signaling cascades and the expression of cytokine genes such as IFN genes.
The present study was initiated to systematically analyze whether any of the ZIKV proteins can interfere with the RIG-I induced IFN-l1 gene expression. For this purpose we cloned all 11 ZIKV genes into a mammalian expression vector. We co-transfected HEK293 cells with constitutively active form of RIG-I, IFN-l1-luciferase reporter-plasmid and ZIKV expression plasmids. The effect of expressed ZIKV protein on RIG-I induced IFN-l1-promoter activation was measured with luciferase assay. We found ZIKV NS2B and especially NS5 proteins to inhibit the RIG-I-mediated activation of IFN-l1 promoter. The mechanism of action for these inhibitory effects is under an intense investigation. ZIKV can also infect primary human monocyte-derived macrophages and dendritic cells (DCs). ZIKV infected DCs show some IFN gene expression, which does, however, remain at a lower level compared to that seen in influenza infection.