The Ran GTPase inhibits SGIV and RGNNV infection by upregulating host immune response in grouper.

Ran is a small G-protein that acts as a "molecular switch" in nucleoplasmic transport regulating cellular activities. However, the functions of Ran in grouper and their effects on the viral infections are still unclear. In this study, we identified and characterized Ran in Epinephelus coioides (EcRan). EcRan encodes a 215 amino acid polypeptide containing key conserved domains including G1-G5 box and C terminal domains. EcRan was widely expressed in different tissues of healthy groupers, and showed obvious nucleus localization. Upon infection of Singapore grouper iridovirus (SGIV) or red spotted grouper nervous necrosis virus (RGNNV), EcRan transcript was significantly decreased. Moreover, overexpression of EcRan remarkably inhibited the replication of SGIV and RGNNV, whereas knockdown of EcRan notably promoted the replication of SGIV and RGNNV. In addition, overexpressed EcRan positively regulated the transcription of interferon (IFN)-related and inflammatory factors, including IFN regulatory factor 3 (IRF3), myxovirus resistance gene 1 (MXI), laboratory of genetics and physiology 2 (LGP2), tumor necrosis factor alpha (TNF-α), tumor necrosis factor receptor-associated factor 6 (TRAF6) and interleukin 8 (IL-8). The transcription of these immune genes was down regulated when EcRan transcription was inhibited by siRNA. Taken together, EcRan showed the antiviral effects against SGIV and RGNNV infections by positively regulating innate immune response.