MAVS splicing variants contribute to the induction of interferon and interferon-stimulated genes mediated by RIG-I-like receptors
- Chen, W.Q., Hu, Y.W., Zou, P.F., Ren, S.S., Nie, P., Chang, M.X.
- Developmental and comparative immunology 49: 19-30 (Journal)
- Registered Authors
- Chang, Mingxian, Nie, Pin
- Antiviral activity, MAVS variants, RIG-I-like receptors, SVCV, Zebrafish
- MeSH Terms
- Adaptor Proteins, Signal Transducing/genetics*
- Adaptor Proteins, Signal Transducing/metabolism
- Alternative Splicing*
- Amino Acid Sequence
- Cell Line
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental/drug effects
- Interferon Type I/genetics*
- Interferon Type I/metabolism
- Interferon Type I/pharmacology
- Microscopy, Fluorescence
- Molecular Sequence Data
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Homology, Amino Acid
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- 25445907 Full text @ Dev. Comp. Immunol.
Chen, W.Q., Hu, Y.W., Zou, P.F., Ren, S.S., Nie, P., Chang, M.X. (2015) MAVS splicing variants contribute to the induction of interferon and interferon-stimulated genes mediated by RIG-I-like receptors. Developmental and comparative immunology. 49:19-30.
The mitochondrial antiviral signaling protein (MAVS) plays a key role in the signal transduction of RIG-I-like receptors (RLRs)-mediated antiviral response. In the present study, zebrafish MAVS transcript variants, namely MAVS_tv1 and MAVS_tv2, were cloned from zebrafish embryos. The putative MAVS_tv1 protein (full length form) contains an N-terminal CARD domain, a central proline region, and a C-terminal transmembrane domain (TM). MAVS_tv2 is generated by a 190 bp intron fragment insertion. The putative MAVS_tv2 protein lacked TM domain due to a frame shift, with the N-terminal 303 aa residues identical to MAVS_tv1, and no sequence homology for the C-terminal 41 aa residues. Real-time PCR showed that the expression of MAVS_tv1 in ZF4 cells was higher than that of MAVS_tv2, and MAVS variants were induced by Edwardsiella tarda and SVCV infection during the early time points of infection, whereas MAVS_tv1 unchanged or MAVS_tv2 decreased at a later time point after the infection, respectively. Overexpression of MAVS_tv1 and MAVS_tv2 in fish cells conferred antiviral resistance, and activated zebrafish IFN1 and IFN3 promoters. MAVS_tv1 overexpression induced a slow (48 hpf) increased expression of IFN1, mxa, mxb, mxe and RSAD2. In contrast, MAVS_tv2 overexpression increased rapidly and transiently the expression of IFN1, IFN2, IFN3, mxc and rsad2 at 6 or 24 hpf. The simultaneous overexpression of MAVS variants and RIG-I in zebrafish embryos led to an accumulative induction of IFNs and IFN-stimulated genes including IFN1, IFN4, mxc, mxe and rsad. Furthermore, MAVS_tv1 cooperated with RIG-I in the accumulation of RIG-I transcript in a positive feedback loop; MAVS_tv2 synergized with MDA5 in the accumulation of MAVS_tv2 transcript. Collectively, these data suggest the molecular mechanisms of fish MAVS variants in antiviral immunity.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes