다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Mitochondrial antiviral-signaling protein (MAVS) transmits signals from RIG-I-like receptors after RNA virus infections. However, the mechanism by which MAVS activates downstream components, such as TBK1 and IKKα/β, is unclear, although previous work suggests the involvement of NEMO or TBK1-binding proteins TANK, NAP1, and SINTBAD. Here, we report that MAVS-mediated innate immune activation is dependent on TRAFs, partially on NEMO, but not on TBK1-binding proteins. MAVS recruited TBK1/IKKe by TRAFs that were pre-associated with TBK1/IKKe via direct interaction between the coiled-coil domain of TRAFs and the SDD domain of TBK1/IKKe. TRAF2−/−3−/−5−/−6−/− cells completely lost RNA virus responses. TRAFs’ E3 ligase activity was required for NEMO activation by synthesizing ubiquitin chains that bound to NEMO for NF-κB and TBK1/IKKe activation. NEMO-activated IKKα/β were important for TBK1/IKKe activation through IKKα/β-mediated TBK1/IKKe phosphorylation. Moreover, individual TRAFs differently mediated TBK1/IKKe activation and thus fine-tuned antiviral immunity under physiological conditions.

/pdf/mavs-activates-tbk1-and-ikke-through-trafs-in-nemo-dependent-2xnyqy9yjq.pdf

MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner.

Summary
Retinoic acid-inducible gene I (RIG-I) -like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG-I, MDA5 and LGP2, together with the downstream molecules such as MITA, TRAF3 and TBK1, have been identified in a range of fish species. However, it is unexpected that RIG-I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of the RIG-I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic dsRNA, poly(I:C), leading to the production of type I interferons (IFNs) and the expression of IFN-stimulated genes (ISGs). Bacterial pathogens, such as Edwardsiella tarda, and their components, such as lipopolysaccharide are also found to induce the expression of RLRs, and whether such induction was mediated through the direct recognition by RLRs or through crosstalk with other pattern recognition receptors recognizing directly bacterial pathogen-associated molecular patterns awaits to be investigated. On the other hand, RLR-activated type I IFN production can be negatively regulated in fish by molecules, such as TBK-1-like protein and IRF10, which are found to negatively regulate RIG-I and MAVS-activated type I IFN production, and to block MITA or bind ISRE motifs, respectively. It is considered that the evolutionary occurrence of RLRs in fish, and their recognized ligands, especially those from their fish pathogens, as well as the mechanisms involved in the RLR signalling pathways, are of significant interest for further investigation.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/imm.12714

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) in fish: current knowledge and future perspectives.

Interferons (IFNs) have been reported in vertebrates from fish to mammals. To date, two types of IFNs, i.e. type I and type II IFNs have been reported in a range of fish species in aquaculture. In fish, type I IFNs are clarified into group I and group II, with two cysteines and four cysteines, and further into subgroups a, d, e, h, and b, c, f, respectively. Group I IFNs appear to exist in all fish species, whereas group II IFNs are discovered only in certain species such as cyprinids, salmonids and perciform fish. It seems preferentially functional that group I IFNs signal through cytokine receptor family B (CRFB) 5 and CRFB1, while group II IFNs through CRFB5 and CRFB2. But they all initiate a same signalling pathway for the expression of interferon induced genes. The information about the production and the function of type I IFNs in fish are further summarized in the review. Interestingly, two members of type II IFNs, IFN-gamma and a unique member, IFN-gamma related gene (IFN-gamma rel) exist in fish, and IFN-gamma and IFN-gamma rel can separately become homodimers for signalling through CRFB13, CRFB17, CRFB6 and CRFB17, respectively. In addition, the variation in the composition of type I and type II IFNs as well as in their receptors in some cyprinid and salmonid fish has also been reviewed. It is suggested that future perspectives for the research on type I and type II IFNs in fish are outlined from a comparative and evolutionary point of view.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/raq.12349

Fish type I and type II interferons: composition, receptor usage, production and function

Identification and characterization of MAVS from black carp Mylopharyngodon piceus.

TBK1 of black carp plays an important role in host innate immune response against SVCV and GCRV.

The antiviral signaling mediated by black carp MDA5 is positively regulated by LGP2

Full length articleTBK1 of black carp plays an important role in host innate immune response against SVCV and GCRV

Characterization of the black carp TRAF6 signaling molecule in innate immune defense

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