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-2induced 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.

Cyprinid herpesvirus‐2 (CyHV‐2): a comprehensive review

“…Lu et al . (2019) reported that CyHV‐2 miR‐C12 suppresses virus‐induced apoptosis and promotes virus replication by targeting caspase 8 and over‐expression of miR‐C12 reduces the expression of caspase 8 and inhibits CyHV‐2 induced apoptosis. Fan et al .…”

“…Very recently, the same team found that, out of the 17 viral miRNAs, CyHV‐2 miR‐C12 is the important suppressor of CyHV‐2‐induced apoptosis of host cells by down regulating caspase 8 expression, promoting viral latency and propagation (Lu et al . 2019). In brief, evidences suggest that CyHV‐2, may become latent and/or persistent in surviving fish after acute infection.…”

“…2018b; Lu et al . 2019). These studies have also provided unique insights into the canonical and non‐canonical roles of miRNAs in the regulation of host and viral gene expression.…”

“…Xia et al (2018) identified and characterized crucian carp IFNc (ccIFNc) ccIFNc as belonging to the type I interferon family with a potential role in countering CyHV-2 infection in crucian carp. Lu et al (2019) reported that CyHV-2 miR-C12 suppresses virus-induced apoptosis and promotes virus replication by targeting caspase 8 and over-expression of miR-C12 reduces the expression of caspase 8 and inhibits CyHV-2 induced apoptosis. Fan et al (2020) cloned and sequenced the complement C3 gene, designated CagC3, from Gibel carp and proved that CagC3 was involved in the innate immune response of Gibel carp to CyHV-2 infection.…”

Integrated analysis of viral miRNAs, mRNA and protein in the caudal fin cells of C. auratus gibelio with cyprinid herpesvirus 2 infection

“…In recent years, some viral miR-NAs encoded by CyHV-2 have been identified in kidney tissue from CyHV-2-infected crucian carp. Among them, miR-C12 attenuated virus-mediated apoptosis and promoted virus replication in host cells by targeting Caspase 8 (Lu et al, 2017(Lu et al, , 2018(Lu et al, , 2019. But research on CyHV-2 virus is still limited.…”