Inter-Organelle Interactions between the ER and Mitotic Apparatus Facilitates Zika Protease Cleavage of Human Kinesin-5 and Contributes to Distinct Mitotic Defects

Abstract

Zika virus infection can result in profound fetal deficits, such as microcephaly and blindness. Here we identify Kif11/Kinesin-5, as a cellular target of Zika protease with both in vitro and in vivo assays. We show that soluble Zika NS2-3 protease chimera targets several sites within the motor domain of HsEg5 either when free in solution or rigor-bound to microtubules. We tested two different forms of the protease in human cells. First, we find that soluble Zika protease chimera is cytotoxic and eventually leads to cell death.