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

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.