In contrast with what was observed with the PERK inhibitor, which decreased microcephaly without interfering with viral replication, treatment with the IRE1α inhibitor 4μ8C resulted in decreased ZIKV replication in the brain and prevented microcephaly in a IFNɑ/β receptor null mouse model, indicating the critical role of IRE1α RNase activity in ZIKV replication and pathogenesis [83]. This evidence concerns the gene ERN1 and microcephaly.