Melanoma differentiation-associated gene 5 in zebrafish provoking higher interferon-promoter activity through signalling enhancing of its shorter splicing variant
- Authors
- Zou, P.F., Chang, M.X., Xue, N.N., Liu, X.Q., Li, J.H., Fu, J.P., Chen, S.N., and Nie, P.
- ID
- ZDB-PUB-131113-8
- Date
- 2014
- Source
- Immunology 141(2): 192-202 (Journal)
- Registered Authors
- Chang, Mingxian, Nie, Pin
- Keywords
- MDA5, MAVS, type IIFN, splicing variant, zebrafish
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/physiology
- Amino Acid Sequence
- Animals
- Cell Line
- DEAD-box RNA Helicases/genetics
- DEAD-box RNA Helicases/metabolism
- DEAD-box RNA Helicases/physiology*
- HEK293 Cells
- Humans
- Interferon Type I/genetics*
- Molecular Sequence Data
- Promoter Regions, Genetic*
- Signal Transduction
- Virus Diseases/prevention & control
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 24116956 Full text @ Immunology
Melanoma differentiation-associated gene 5 (MDA5) is one of the three members in the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which are cytoplasmic pathogen recognition receptors (PRRs) recognizing intracellular viruses. In the present study, MDA5 and its spliced shorter form, named as MDA5a and MDA5b were identified in zebrafish. MDA5a and MDA5b can be all up-regulated in cell line following the infection of a negative ssRNA virus, the Spring viremia of carp virus (SVCV) and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, implying that the RLR may also be able to sense elements released from bacteria. The overexpression of MDA5a and MDA5b in fish cells resulted in significant induction of type I IFN promoter activity and enabled the protection of transfected cells against SVCV infection. Furthermore, the shorter spliced form, MDA5b when co-transfected with MDA5a or MAVS, induced a significantly higher level of IFN promoter activity, indicating that MDA5b may function as an enhancer in the interaction between MDA5 and MAVS.