Cyprinid Herpesvirus 2 miR-C12 Attenuates Virus-Mediated Apoptosis and Promotes Virus Propagation by Targeting Caspase 8.

Jianfei Lu,Liqun Lu,Zhaoyuan Shen,Dan Xu

doi:10.3389/fmicb.2019.02923

Abstract

DNA viruses, most notably members of the herpesvirus family, generally encode miRNAs to mediate both virus and host genes expression. We previously demonstrated that Cyprinid herpesvirus 2 (CyHV-2) encodes 17 miRNAs that are involved in innate immune signaling pathways. In this study, the function of CyHV-2-encoded miRNA was further investigated in GiCF cells. We found that miR-C4 promoted CyHV-2-induced apoptosis, while miR-C12 decreased CyHV-2-induced apoptosis. miR-C12 targeted to 3′ UTR sequence of caspase 8 and suppressed the expression of caspase 8. Besides, the silencing of caspase 8 by specific siRNA led to the attenuation of CyHV-2-induced apoptosis. Furthermore, caspase 8 was downregulated in cells transfected with miR-C12 during CyHV-2 infection. Overexpression of miR-C12 significantly suppressed CyHV-2-induced apoptosis, while silencing of miR-C12 promoted CyHV-2-induced apoptosis. Finally, inhibition of miR-C12 resulted in suppression of CyHV-2 propagation, overexpression of miR-C12, and CASP8-siRNA-1 facilitated CyHV-2 propagation. Taken together, our results demonstrated that CyHV-2-encoded miR-C12 to suppress virus-induced apoptosis and promoted virus replication by targeting caspase 8.

Highlights

The Alloherpesviridae is a family of double-stranded DNA viruses that infect amphibians and fish, which comprises of four genera: Batrachovirus, Cyprinivirus, Icta-lurivirus, and Salmonivirus
A novel cell line (Carassius auratus gibelio caudal fin cell line, GiCF) permission to Cyprinid herpesvirus 2 (CyHV-2) replication was established, and we demonstrated that CyHV-2 infection induces GiCF cell apoptosis (Lu et al, 2018a)
We found that miR-C4 promotes CyHV-2-induced apoptosis, while miR-C12 decreases CyHV-2-induced apoptosis

Summary

Introduction

The Alloherpesviridae is a family of double-stranded DNA viruses that infect amphibians and fish, which comprises of four genera: Batrachovirus, Cyprinivirus, Icta-lurivirus, and Salmonivirus. Many reports have demonstrated that Cyprinivirus, mainly CyHV-2 and CyHV-3, can lead to latent infection (Reed et al, 2014; Wei et al, 2019), produce virus-encoded MicroRNAs (Donohoe et al, 2015; Lu et al, 2017), and facilitate viral invasion by exploiting miR-C12 Regulates Apoptosis various intracellular signaling pathways (Adamek et al, 2014; Zhou et al, 2019). Some studies reported that many different herpesviruses regulate apoptosis in infected cells (Miest et al, 2014; Scrochi et al, 2017; You et al, 2017). A novel cell line (Carassius auratus gibelio caudal fin cell line, GiCF) permission to CyHV-2 replication was established, and we demonstrated that CyHV-2 infection induces GiCF cell apoptosis (Lu et al, 2018a)

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