American-Asian- and African lineages of Zika virus induce differential pro-inflammatory and Interleukin 27-dependent antiviral responses in human monocytes

•Human monocytes are more susceptible to infection with ZIKV from Colombia (American-Asian lineage) than ZIKV from Dakar (African lineage).•American-Asian- lineages (ZIKV Colombia and ZIKV Puerto Rico) activated the IL27 signaling and induced a robust antiviral response in an IFN-independent manner.•IL27 treatment of human monocytes led to a strongly decreased release of ZIKV from Colombia in a dose-dependent manner, compared to ZIKV from Dakar.•ZIKV Puerto Rico strain promotes a higher pro-inflammatory response TLR2-dependent and the NF-κB complex activation than ZIKV Nigeria strain.•The findings highlight the differential inflammatory response and antiviral activity of monocytes infected with different lineages of ZIKV.