Abstract

Understanding how infected cells respond to Ebola virus (EBOV) and how this response changes during the process of viral replication and transcription are very important for establishing effective antiviral strategies. In this study, we conducted a genome-wide screen to identify long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), micro RNAs (miRNAs), and mRNAs differentially expressed during replication and transcription using a tetracistronic transcription and replication-competent virus-like particle (trVLP) system that models the life cycle of EBOV in 293T cells. To characterize the expression patterns of these differentially expressed RNAs, we performed a series cluster analysis, and up- or down-regulated genes were selected to establish a gene co-expression network. Competing endogenous RNA (ceRNA) networks based on the RNAs responsible for the effects induced by EBOV replication and transcription in human cells, including circRNAs, lncRNAs, miRNAs, and mRNAs, were constructed for the first time. Based on these networks, the interaction details of circRNA-chr19 were explored. Our results demonstrated that circRNA-chr19 targeting miR-30b-3p regulated CLDN18 expression by functioning as a ceRNA. These findings may have important implications for further studies of the mechanisms of EBOV replication and transcription. These RNAs potentially have important functions and may be promising targets for EBOV therapy.

Highlights

  • Ebola virus (EBOV) causes a severe hemorrhagic fever, and EBOV-related experiments must be performed under biosafety level (BSL) 4 conditions

  • We identified 342 long non-coding RNAs (lncRNAs), 26 circRNAs, 468 mRNAs and 199 micro RNAs (miRNAs) that were differentially expressed between 24 and 0 h; 389 lncRNAs, 56 circRNAs, 425 mRNAs and 209 miRNAs between 48 and 0 h; 177 lncRNAs, 33 circRNAs, 233 mRNAs, and 252 miRNAs between 72 and 0 h; and 1,858 lncRNAs, 125 circRNAs, 1,911 mRNAs and 317 miRNAs between 96 and 0 h (P < 0.05, fold change > 2) (Tables S1–S4)

  • We conducted a genome-wide search for Competing endogenous RNA (ceRNA) that may be responsible for the effects induced by EBOV infection and replication in human cells

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Summary

Introduction

Ebola virus (EBOV) causes a severe hemorrhagic fever, and EBOV-related experiments must be performed under biosafety level (BSL) 4 conditions. After pretransfection with EBOV NP, VP35, VP30, and L expression vectors, the cells can be infected by the trVLPs. the trVLP system can be used as a tool to explore the cellular mechanism changes related to EBOV replication, transcription, morphogenesis, budding, and entry (Hoenen et al, 2014). The trVLP system was used to perform a rapid screening assay of effective viral polymerase inhibitors of EBOV, and the anti-EBOV activity of the selected drugs was confirmed using fully infectious Zaire EBOV, indicating that this system can be used for studies of virus replication and the development of novel antivirals (McCarthy et al, 2016; Biedenkopf and Hoenen, 2017)

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