Rui Wang

Introduction. Zika Virus (ZIKV) is a mosquito-born enveloped ssRNA flavivirus first recognized in humans in 1953 and has since led to the 2015-2016 epidemic in the Americas^1,2. ZIKV has been associated with congenital microcephaly with presentations of cerebral lesions, appearance of collapsed skull, skin redundancy, and fetal brain disruption sequence³. There are a variety of transmission route including sexual contact, blood transfusion and prenatal from mother to fetus². Studies have shown that placental transmission of ZIKV occurs through infection of placental macrophage inducing production of type I interferon and pro-inflammatory cytokines resulting in antiviral gene expression². Additional AXL receptor tyrosine kinase has been found to be particularly vulnerable to ZIKV infection and may play a role in mediating infection⁴. Gaining an understanding of the mechanism of entry by ZIKV provide strategies for therapeutic approach. Methods. Neonatal mice lacking type 1 interferon were given an intraocular injection of ZIKV and high-titer anti-ZIKV antiserum was used to detect fluorescence⁵. Human induced pluripotent stem cells (hiPSCs) were incubated with titer of ZIKV and infectivity, caspase-3 activity, and global transcriptome analyses were conducted⁶. Results. In neonatal mice, widespread but sparse infection throughout multiple brain regions were observed with glial cells demonstrating productive infection producing new ZIKV progeny by 24 hours after inoculation⁵. AXL was found to be widely expressed in microglia and astrocyte and mediated ZIKV endocytosis with Gas6 ligand involvement⁴. In neonatal mice, astrocytes were identified as the first cells targeted by ZIKV and the route of viral movement within the brain involve axonal transport to synaptically coupled brain loci⁵. ZIKV efficiently infected hNPCs and induced productive release of infectious ZIKV particles by upregulating apoptosis and dysregulating cell-cyle progression resulting in attenuated hNPC growth⁶. Conclusions. Astrocytes typically contribute to the maintenance of blood brain barrier (BBB) and the early infection by ZIKV may induce BBB leakage contributing to release of pro-inflammatory cytokines leading to microcephaly^7,8. The role of AXL during ZIKV infection of glial cells allow inhibition of AXL as a potential target for future antiviral therapies. In particular, MYD1 is an engineered Axl decoy receptor that displays a high affinity for human Gas6 and has been found to effectively block the ligand-receptor interaction of ZIKV in a dose-dependent manner⁴.

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