title: Fish TRIM39 regulates cell cycle progression and exerts its antiviral function against iridovirus and nodavirus.
abstract: The tripartite motif (TRIM)-containing proteins exert important immune regulatory roles through regulating different signaling pathways in response to different stimuli. TRIM39, a member of the TRIM family, is a RING domain-containing E3 ubiquitin ligase which could regulate cell cycle progression and apoptosis. However, the antiviral activity of TRIM39 is not explored. Here, a TRIM39 homolog from grouper, Epinephelus coioides (EcTRIM39) was cloned, and its effects on cell cycle progression and fish virus replication were investigated. The full-length EcTRIM39 cDNA was composed of 2535 bp and encoded a polypeptide of 543 amino acids with 70% identity with TRIM39 homologs from bicolor damselfish. Amino acid alignment analysis indicated that EcTRIM39 contained a RING finger, B-box and SPRY domain. Expression profile analysis revealed that EcTRIM39 was abundant in intestine, spleen and skin. Upon different stimuli in vivo, the EcTRIM39 transcript was obviously up-regulated after challenging with Singapore grouper iridovirus (SGIV), and polyinosinic-polycytidylic acid (poly I:C). Using fluorescence microscopy, we found that EcTRIM39 localized in the cytoplasm and formed aggregates in grouper spleen (GS) cells. The ectopic expression of EcTRIM39 in vitro affected the cell cycle progression via mediating G1/S transition. Moreover, the RING domain was essential for its accurate localization and effect on cell cycle. In addition, overexpression of EcTRIM39 significantly inhibited viral gene transcription of SGIV and red-spotted grouper nervous necrosis virus (RGNNV) in vitro, and the mutant of RING exerted the opposite effect. Together, our results demonstrated that fish TRIM39 not only regulated the cell cycle progression, but also acted as an important regulator of fish innate immune response against viruses.
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Yepin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory Breeding Base for Sustainable Exploitation of Tropical Biotic Resources, College of Marine Science, Hainan University, Haikou, 570228, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Songwei
authors.initials: S
authors.lastname: Ni
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China. Electronic address: qinqw@scsio.ac.cn.
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China. Electronic address: huangxh@scsio.ac.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001492:Bass; D003001:Cloning, Molecular; D004266:DNA Virus Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005393:Fish Diseases / Q000235:genetics* / Q000276:immunology / Q000821:virology; D029941:Fish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017994:Iridovirus / Q000502:physiology; D030381:Nodaviridae / Q000502:physiology; D010802:Phylogeny; D011070:Poly I-C / Q000494:pharmacology*; D012327:RNA Virus Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment / Q000662:veterinary; D000070584:Tripartite Motif Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D029941:Fish Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; D011070:Poly I-C
keywords: Antiviral; Cell cycle; Grouper; TRIM39; Viral replication