Zika Virus Dysregulates The Expression Of Astrocytic Genes Involved In Neurodevelopment

Zika virus(ZIKV)is a kind of flavivirus that has led to a worldwide public health concern since 2016.ZIKV emerged in French Polynesia and Brazil causes various neurological conditions,which are associated with fetus brain development or peripheral and central nervous systems(PNS/CNS)functional problems.To date,no antiviral therapy or vaccine against ZIKV infection is available.It urgently needs efforts to explore the underlying molecular mechanisms of ZIKV-induced neural pathogenesis.Astrocytes are the brains` enriched cell type with a 1:3 ratio to neurons in the rats and mice cortex,whereas 1:4 per neuron in the human cortex.Broad-spectrum functions of astrocytes have gain interest in recent years,including providing metabolic and structural support to neurons,guiding the developing axons migration,synaptic transmission,certain neuroblasts during development,neurodevelopment,astrocytes conversion to neurons,and response to injury.ZIKV favorably infects neural and glial cells specifically astrocytes,consequently dysregulating gene expression and pathways with impairment of process neural cells.In this study,we applied a model for ZIKV replication in mouse primary astrocytes(MPAs)and profiled temporal alterations in the host transcriptomes upon ZIKV infection.Among RNA-sequencing data of 27,812 genes,we examined 710 genes that were significantly differentially expressed by ZIKV,leading to dysregulation of numerous functions including neurons development and migration,glial cells differentiation,myelinations,astrocytes projection,neurogenesis,and brain development,along with multiple pathways including tight junction,PI3K-Akt signaling pathway,Hippo signaling pathway,and focal adhesion.Furthermore,we confirmed the dysregulation of the selected genes in MPAs and human astroglioma U251 cells by RT-q PCR,and results illustrated that the selected gene expression profiles were accordant with obtained results of RNA-Seq,concluding its accuracy and reproducibility.It was represented that PTBP1,LIF,GHR,and PTBP3 were upregulated while EDNRB and MBP were downregulated upon ZIKV infection.This study highlights the ZIKV-mediated potential genes associated with neurodevelopment or related diseases.In conclusion,the alteration of astrocytic gene functions or associated pathways suggests a novel clue of a mechanism involved in ZIKV-induced neurodevelopment diseases.