Fish TRIM16L exerts negative regulation on antiviral immune response against grouper iridoviruses.
Tripartite motif 16 (TRIM16), has been demonstrated to act as a tumor suppressor through affecting cell proliferation and migration or tumorigenicity in carcigenesis. However, the roles of TRIM16 in immune response were unknown up to now. Here, we cloned a TRIM16-like gene (TRIM16L) from orange spotted grouper (EcTRIM16L) and investigated its roles in response to virus infection. EcTRIM16L encoded a 478 amino acid peptide which showed 72% and 29% identity to large yellow croaker (Larimichthys crocea) and human (Homo sapiens), respectively. Sequence alignments indicated that EcTRIM16L shared the different gene structures with human TRIM16, evidenced by the presence of RING domain, but absence of the B-box domain. In transfected grouper cells, the green fluorescence mainly distributed in cytoplasm, and the deletion of SPRY domain affected the accurate localization of EcTRIM16L. In response to different stimuli, including infection with Singapore grouper iridovirus (SGIV) or red-spotted grouper nervous necrosis (RGNNV), and transfection with b-DNA or poly I:C, the transcript of EcTRIM16L were differently regulated in grouper spleen cells. After incubation with SGIV, the ectopic expression of EcTRIM16L significantly enhanced the viral replication, demonstrated by the increase of cytopathic effect (CPE) severity and viral gene transcriptions. Simultaneously, we also found that overexpression of EcTIRM16L in vitro significantly weakened the expression of interferon related molecules, including interferon regulatory factor 3 (IRF3), IRF7, and melanoma differentiation-associated protein 5 (MDA5). Moreover, the ectopic expression of EcTRIM16L significantly decreased both MDA5-and mediator of IRF3 activation (MITA)-induced interferon immune responses. Further studies showed that the RING domain played more important roles in the molecular action of EcTIRM16L during grouper virus infection. Our data, for the first time, demonstrated that fish TRIM16L exerted negative regulation on the interferon immune response against DNA virus infection.
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; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China; University of Chinese Academy of Sciences, Beijing, China.
Yepin
Y
Yu
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; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China; University of Chinese Academy of Sciences, Beijing, China.
Xiaohong
X
Huang
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; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China; University of Chinese Academy of Sciences, Beijing, China.
Jingcheng
J
Zhang
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; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China; University of Chinese Academy of Sciences, Beijing, China.
Jiaxi
J
Liu
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; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China; University of Chinese Academy of Sciences, Beijing, China.
Yin
Y
Hu
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; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China; University of Chinese Academy of Sciences, Beijing, China.
Ying
Y
Yang
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; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China.
Jia
J
Cai
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; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: huangyh@scsio.ac.cn.
Youhua
Y
Huang
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; Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China; University of Chinese Academy of Sciences, Beijing, China; College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China. Electronic address: qinqw@scsio.ac.cn.
Qiwei
Q
Qin
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 / Q000276:immunology; D007113:Immunity, Innate; D010802:Phylogeny; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017995:Ranavirus / Q000502:physiology; D016415:Sequence Alignment / Q000662:veterinary; D000070584:Tripartite Motif Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*
D018076:DNA, Complementary; D029941:Fish Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; D011070:Poly I-C
Grouper; Interferon; Iridovirus; TRIM16L; Viral replication