Examination of the ZIKV pathogenesis in the Human Fetal Brain

Abstract

Zika virus (ZIKV) is a single-stranded RNA virus of the Flaviviridae family, genus Flavivirus. Infection with ZIKV is associated with severe neurological disorders and congenital deformities like microcephaly. Even though outbreaks of ZIKV have been reported worldwide the mode of entry and the mechanism of action of this virus still remains unclear. The cellular receptors and determinants that mediate entry of ZIKV in the human fetal brain are still unclear. Previous studies have reported that AXL,TYRO-3,MERTK and TIM-1 receptors aid in the ZIKV entry to the human body. This study focuses on analyzing the presence of these receptors in the human fetal brain. We performed RT-PCR and RNA sequencing which showed an increased expression of AXL and TYRO-3 receptors in the brain samples infected with ZIKV for 3 and 4 days as compared to the infected aged- matched samples. RNA sequencing analysis revealed differential expression of the receptors previously known to be involved in Flavivirus entry. A slight increase in expression of these receptors was observed in the brain samples infected with ZIKV for 3 and 4 days as compared to the uninfected brain tissue samples. This finding provided further evidence for involvement of AXL, MERTK, and TYRO3 receptors in ZIKV infection in the human fetal brain and provided insights into the ZIKV host interactions. Interestingly, RNA sequencing analysis revealed the key biological pathways related to immune system response, negative regulation of viral processes, apoptosis and autophagy that were affected by infection. These findings provided insights in the molecular signatures associated with ZIKV infection. Further studies could potentially reveal the cellular responses that can be targeted to develop antiviral drugs and other related therapies to prevent ZIKV infection.