AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses

• DOI: 10.1073/pnas.1620558114
• Publication Date: 2017-02-07T02:05:30Z
• Authors: Audrey Stéphanie ...; Byoung-Shik Shim; Young-Chan Kwon; Rong Zhang; Yuka Otsuka; Kimberly Schmitt; Fatma Berri; Michael S. Diamond; Hyeryun Choe
• Keywords: Zika Virus; GAS6; Microcephaly; Flavivirus

Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, the closely related dengue (DENV) or West Nile (WNV), can efficiently infect key placental barrier cells directly contact fetal bloodstream. We AXL, receptor tyrosine kinase, is primary ZIKV entry cofactor on human umbilical vein endothelial (HUVECs), uses AXL with much greater efficiency than does DENV WNV. Consistent this observation, only WNV DENV, bound ligand Gas6. In comparison, were insect they also infected HUVECs an AXL-dependent manner. Our data suggest from infects more flaviviruses because binds Gas6 avidly, which turn facilitates its interaction AXL.