SciCombinator

Discover the most talked about and latest scientific content & concepts.

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

OPEN Proceedings of the National Academy of Sciences of the United States of America | 9 Feb 2017

AS Richard, BS Shim, YC Kwon, R Zhang, Y Otsuka, K Schmitt, F Berri, MS Diamond and H Choe
Abstract
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, ZIKV, but not the closely related dengue virus (DENV) or West Nile virus (WNV), can efficiently infect key placental barrier cells that directly contact the fetal bloodstream. We show that AXL, a receptor tyrosine kinase, is the primary ZIKV entry cofactor on human umbilical vein endothelial cells (HUVECs), and that ZIKV uses AXL with much greater efficiency than does DENV or WNV. Consistent with this observation, only ZIKV, but not WNV or DENV, bound the AXL ligand Gas6. In comparison, when DENV and WNV were produced in insect cells, they also infected HUVECs in an AXL-dependent manner. Our data suggest that ZIKV, when produced from mammalian cells, infects fetal endothelial cells much more efficiently than other pathogenic flaviviruses because it binds Gas6 more avidly, which in turn facilitates its interaction with AXL.
Tweets*
27
Facebook likes*
4
Reddit*
0
News coverage*
15
Blogs*
4
SC clicks
0
Concepts
Fetus, Centers for Disease Control and Prevention, Viruses, Flaviviridae, Ribavirin, Flaviviruses, Infection, West Nile virus
MeSH headings
-
comments powered by Disqus

* Data courtesy of Altmetric.com