Functional characterization of short-isoform of PARP12 in the immune response to SVCV infection in common carp (Cyprinus carpio).

Abstract

Poly(ADP-ribose) polymerase 12 (PARP12), which has been identified as an interferon-stimulated gene (ISG), is able to restrict virus replication via PARP-dependent ADP-ribosylation of target molecules. Presently, the antiviral abilities of PARP12 have been reported in mammalian organisms, whereas no data is available on the immune function of PARP12 in fish species. In the present study, a PARP12 gene (CcPARP12) was identified from common carp (Cyprinus carpio), and its role in antiviral immune response was investigated. Structurally, CcPARP12 was shown to consist of ZnF-C3H1 motifs and WWE domain, which was in line with PARP12-short (S) isoform in domain architecture. In vivo gene expression analysis showed that CcPARP12 mRNA expression levels were varied in various tissues of healthy carps with the highest level in head kidney, and spring viraemia of carp virus (SVCV) induced CcPARP12 expression in multiple immune-related tissues. Analysis of subcellular localization showed that CcPARP12 was located in the nucleus region of EPC cells. Additionally, in vitro, it was shown that CcPARP12 could affect SVCV replication in EPC cells, with reduced virus load and relieved cytopathic effects (CPEs), and moreover positively regulated the expressions of antiviral molecules ISG15, IFN and Viperin in response to SVCV infection. Overall, these results indicated that CcPARP12 could play the defensive role in the host immune response to SVCV infection. This study has broadened the understanding of antiviral properties of PARP12 in fish species and even lower vertebrates, providing potential new therapeutic targets against SVCV infection.