Ubiquitination and deubiquitination have emerged as critical regulatory processes in the virus-triggered type I interferon (IFN) induction pathway. In this study, we carried out a targeted siRNA screen of 54 ubiquitin-specific proteases (USPs) and identified USP25 as a negative regulator of the virus-triggered type I IFN signaling pathway. Overexpression of USP25 inhibited virus-induced activation of IFN-β, interferon regulation factor 3 (IRF3) and nuclear factor-kappa B (NF-κB), as well as the phosphorylation of IRF3 and NF-κB subunit p65. Furthermore, Knockdown of USP25 potentiated virus-induced induction of the IFN-β. In addition, detailed analysis demonstrated that USP25 cleaved lysine 48- and lysine 63-linked polyubiquitin chains in vitro and in vivo, and its deubiquitinating enzyme (DUB) activity, were dependent on a cysteine residue (Cys178) and a histidine residue (His607). USP25 mutants lacking DUB activity lost the ability to block virus-induced type I IFN to some degree. Mechanistically, USP25 deubiquitinated retinoic acid-inducible gene I (RIG-I), tumornecrosis factor (TNF) receptor-associated factor 2 (TRAF2), and TRAF6 to inhibit RIG-I-like receptor-mediated IFN signaling. Our findings suggest that USP25 is a novel DUB negatively regulating virus-induced type I IFN production.
Development of embryos and larvae in the common Japanese conger Conger myriaster was observed after artificial fertilization. Eggs were obtained from females matured artificially by hormone injections and milt was obtained from males matured naturally. Fertilized eggs were kept in seawater at 12–14°C. The first cleavage occurred at 4 h, epiboly began at 24 h, the embryonic body was formed at 38 h and hatching occurred at 84 h after insemination. Newly hatched larvae were approximately 2.5 mm (total length) and similar to those of Anguilla japonica in terms of external features. The mouth and anus opened on the 7th day after hatching. Pigments began to appear at the tip of the tail on the 10th day. The total length of the larvae reached approximately 8 mm on the 11th day. Eye pigmentation began on the 14th day. One larva lived for 19 days without food.
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