ZIKV infection effects changes in gene splicing, isoform composition and lncRNA expression in human neural progenitor cells

Benxia Hu,Yongxia Huo,Minhua Luo,Guijun Chen,Jinlong Yang,Jumin Zhou,Liping Yang

doi:10.1186/s12985-017-0882-6

Abstract

BackgroundThe Zika virus (ZIKV) is a mosquito-borne flavivirus that causes microcephaly and Guillain-Barré syndrome in infected individuals. To obtain insights into the mechanism of ZIKV infection and pathogenesis, we analyzed the transcriptome of ZIKV infected human neural progenitor cells (hNPCs) for changes in alternative splicing (AS), gene isoform (ISO) composition and long noncoding RNAs (lncRNAs) expression.MethodsWe analyzed differentially expressed lncRNAs, AS, ISO from RNA-seq data in ZIKV infected hNPCs.ResultsWe obtained 149 differentially expressed lncRNAs, including potential viral targets to modulate cellular processes such as cell cycle, apoptosis and immune response. The infection induced 262 cases of AS occurring in 229 genes, which were enriched in cell death, RNA processing, transport, and neuron development. Among 691 differentially expressed ISOs, upregulated ISOs were enriched in signaling, regulation of transcription, and amino acid biosynthesis, while downregulated ISOs were mostly enriched in cell cycle. Importantly, these analyses revealed specific links between ZIKV induced changes in cellular pathways and the type of changes in the host transcriptome, suggesting important regulatory mechanisms.ConclusionsOur analyses revealed candidate lncRNAs, AS events and ISOs which may function in ZIKV infection induced cell cycle disruption, apoptosis and attenuation of neurogenesis, and shed light on the roles of lncRNAs, AS and ISOs in virus-host interactions, and would facilitate future studies of ZIKV infection and pathogenesis.

Highlights

The Zika virus (ZIKV) is a mosquito-borne flavivirus that causes microcephaly and Guillain-Barré syndrome in infected individuals
These results indicated that ZIKV infection induced significant changes in alternative splicing (AS), ISOs and Long noncoding RNA (lncRNA) expression, which could play key roles in ZIKV infection, virushost interactions, and pathogenesis
Expressed lncRNAs in ZIKV infected human neural progenitor cells (hNPCs) To generate a compendium of all annotated and novel lncRNAs that exhibited differential expression in ZIKV infected hNPCs, we analyzed RNA-seq data generated by using a low multiplicity of infection (MOI < 0.1) of MR766 strain of the ZIKV (African lineage) to infect hNPCs for 56 h [6]

Summary

Introduction

The Zika virus (ZIKV) is a mosquito-borne flavivirus that causes microcephaly and Guillain-Barré syndrome in infected individuals. Zika virus (ZIKV) is a positive-strand RNA virus with a 10,800 nucleotides genome, belonging to the Flaviviridae family and the genus Flavivirus [1]. It includes African and Asian lineages, and could be transmitted by Aedes species mosquitoes, sex, blood transfusion, organ transplantation, and potentially through urine or saliva [2]. A cellular lncRNA, ncRNA repressor of the nuclear factor of activated T cells (NRON), degrades the Tat protein, and contributes to HIV-1 latency [14]

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Conclusion