Determination of System Level Alterations in Host Transcriptome Due to Zika Virus (ZIKV) Infection in Retinal Pigment Epithelium

Overview

Journal Sci Rep

Specialty Science

Date 2018 Jul 27

PMID 30046058

Citations 28

Authors

Pawan Kumar Singh

Indu Khatri

Alokkumar Jha

Carla D Pretto

Katherine R Spindler

Vaithilingaraja Arumugaswami

Shailendra Giri

Ashok Kumar

Manoj K Bhasin

Affiliations

Soon will be listed here.

Abstract

Previously, we reported that Zika virus (ZIKV) causes ocular complications such as chorioretinal atrophy, by infecting cells lining the blood-retinal barrier, including the retinal pigment epithelium (RPE). To understand the molecular basis of ZIKV-induced retinal pathology, we performed a meta-analysis of transcriptome profiles of ZIKV-infected human primary RPE and other cell types infected with either ZIKV or other related flaviviruses (Japanese encephalitis, West Nile, and Dengue). This led to identification of a unique ZIKV infection signature comprising 43 genes (35 upregulated and 8 downregulated). The major biological processes perturbed include SH3/SH2 adaptor activity, lipid and ceramide metabolism, and embryonic organ development. Further, a comparative analysis of some differentially regulated genes (ABCG1, SH2B3, SIX4, and TNFSF13B) revealed that ZIKV induced their expression relatively more than dengue virus did in RPE. Importantly, the pharmacological inhibition of ABCG1, a membrane transporter of cholesterol, resulted in reduced ZIKV infectivity. Interestingly, the ZIKV infection signature revealed the downregulation of ALDH5A1 and CHML, genes implicated in neurological (cognitive impairment, expressive language deficit, and mild ataxia) and ophthalmic (choroideremia) disorders, respectively. Collectively, our study revealed that ZIKV induces differential gene expression in RPE cells, and the identified genes/pathways (e.g., ABCG1) could potentially contribute to ZIKV-associated ocular pathologies.

Citing Articles

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