1. Academic Validation
  2. Methyltransferase-like 3 suppresses red spotted grouper nervous necrosis virus and viral hemorrhagic septicemia virus infection by enhancing type I interferon responses in sea perch

Methyltransferase-like 3 suppresses red spotted grouper nervous necrosis virus and viral hemorrhagic septicemia virus infection by enhancing type I interferon responses in sea perch

  • Fish Shellfish Immunol. 2023 Aug 16;140:108993. doi: 10.1016/j.fsi.2023.108993.
Lan Yao 1 Wanwan Zhang 1 Xiaoqi Chen 1 Meisheng Yi 2 Kuntong Jia 3
Affiliations

Affiliations

  • 1 School of Marine Sciences, Sun Yat-sen University, Guangzhou, 510000, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, 510000, China; Pearl River Estuary Marine Ecosystem Research Station, Ministry of Education, Zhuhai, 519000, China.
  • 2 School of Marine Sciences, Sun Yat-sen University, Guangzhou, 510000, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, 510000, China; Pearl River Estuary Marine Ecosystem Research Station, Ministry of Education, Zhuhai, 519000, China. Electronic address: yimsh@mail.sysu.edu.cn.
  • 3 School of Marine Sciences, Sun Yat-sen University, Guangzhou, 510000, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, 510000, China; Pearl River Estuary Marine Ecosystem Research Station, Ministry of Education, Zhuhai, 519000, China. Electronic address: jiakt3@mail.sysu.edu.cn.
Abstract

Methylation at the N6 position of adenosine (m6A) is the most abundant internal mRNA modification in eukaryotes, tightly associating with regulation of viral life circles and immune responses. Here, a methyltransferase-like 3 homolog gene from sea perch (Lateolabrax japonicus), designated LjMETTL3, was cloned and characterized, and its negative role in fish virus pathogenesis was uncovered. The cDNA of LjMETTL3 encoded a 601-amino acid protein with a MT-A70 domain, which shared the closest genetic relationship with Echeneis naucrates METTL3. Spatial expression analysis revealed that LjMETTL3 was more abundant in the immune tissues of sea perch post red spotted grouper nervous necrosis virus (RGNNV) or viral hemorrhagic septicemia virus (VHSV) Infection. LjMETTL3 expression was significantly upregulated at 12 and 24 h post RGNNV and VHSV Infection in vitro. In addition, ectopic expression of LjMETTL3 inhibited RGNNV and VHSV Infection in LJB cells at 12 and 24 h post Infection, whereas knockdown of LjMETTL3 led to opposite effects. Furthermore, we found that LjMETTL3 may participate in boosting the type I interferon responses by interacting with TANK-binding kinase. Taken together, these results disclosed the Antiviral role of fish METTL3 against RGNNV and VHSV and provided evidence for understanding the potential mechanisms of fish METTL3 in Antiviral innate immunity.

Keywords

IFNh; Methyltransferase-like 3; RGNNV; Sea perch; TBK1; VHSV.

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