Oncorhynchus mykiss OmTRIM25 activates the interferon-1 pathway and positively regulates the antiviral innate immune response to infectious hematopoietic necrosis virus

Abstract

Tripartite motif proteins (TRIM) are found in all multicellular organisms and participate in regulating a wide range of life activities. Among them, TRIM25 proteins play a crucial role in antiviral innate immunity. In this study, TRIM25 from rainbow trout, Oncorhynchus mykiss (OmTRIM25) was cloned and its effect on infectious hematopoietic necrosis virus (IHNV) replication was investigated. OmTRIM25 encodes 495 amino acids containing RING, B-BOX2, a Coiled-Coil domain, and a PRY domain. After infection with IHNV, the expression of OmTRIM25 in blood, the intestine, gills, and mucus greatly increased. OmTRIM25 was determined to exhibit E3 ubiquitin ligase activity by immunoprecipitation and was dependent on Lys63 linked for poly-ubiquitination modifications. Overexpression of OmTRIM25 has inhibited the replication of IHNV, as justified by a significant reduction in IHNV gene copies. Meanwhile, OmTRIM25 can activate interferon-1 (IFN-1) transcription, and this activation is dependent on the RING domain of OmTRIM25. In addition, OmTRIM25 can upregulate the expression levels of cytokines such as mitochondrial antiviral signaling protein (MAVS), IFN-1, and interleukin 6/8 (IL-6/8). In conclusion, our results suggest that OmTRIM25 can promote the activation of IFN-1 and regulate the expression of interferon-related transcription factors and inflammatory cytokines against IHNV.