PUBLICATION
Bmp4 in Zebrafish Enhances Antiviral Innate Immunity through p38 MAPK (Mitogen-Activated Protein Kinases) Pathway
- Authors
- Chen, L., Zhong, S., Wang, Y., Wang, X., Liu, Z., Hu, G.
- ID
- ZDB-PUB-231015-61
- Date
- 2023
- Source
- International Journal of Molecular Sciences 24(19): (Journal)
- Registered Authors
- Liu, Zhenhui
- Keywords
- BMP4, IFN, antiviral innate immunity, p38 MAPK pathway, zebrafish
- MeSH Terms
-
- Animals
- Bone Morphogenetic Proteins*/metabolism
- Immunity, Innate*
- Mitogen-Activated Protein Kinases
- Reoviridae/physiology
- Virus Diseases/genetics
- Zebrafish*/genetics
- Zebrafish*/metabolism
- p38 Mitogen-Activated Protein Kinases/genetics
- p38 Mitogen-Activated Protein Kinases/metabolism
- PubMed
- 37833891 Full text @ Int. J. Mol. Sci.
Citation
Chen, L., Zhong, S., Wang, Y., Wang, X., Liu, Z., Hu, G. (2023) Bmp4 in Zebrafish Enhances Antiviral Innate Immunity through p38 MAPK (Mitogen-Activated Protein Kinases) Pathway. International Journal of Molecular Sciences. 24(19):.
Abstract
Bone morphogenetic proteins (BMPs) are a group of structurally and functionally related signaling molecules that comprise a subfamily, belonging to the TGF-β superfamily. Most BMPs play roles in the regulation of embryonic development, stem cell differentiation, tumor growth and some cardiovascular and cerebrovascular diseases. Although evidence is emerging for the antiviral immunity of a few BMPs, more BMPs are needed to determine whether this function is universal. Here, we identified the zebrafish bmp4 ortholog, whose expression is up-regulated through challenge with grass carp reovirus (GCRV) or its mimic poly(I:C). The overexpression of bmp4 in epithelioma papulosum cyprini (EPC) cells significantly decreased the viral titer of GCRV-infected cells. Moreover, compared to wild-type zebrafish, viral load and mortality were significantly increased in both larvae and adults of bmp4-/- mutant zebrafish infected with GCRV virus. We further demonstrated that Bmp4 promotes the phosphorylation of Tbk1 and Irf3 through the p38 MAPK pathway, thereby inducing the production of type I IFNs in response to virus infection. These data suggest that Bmp4 plays an important role in the host defense against virus infection. Our study expands the understanding of BMP protein functions and opens up new targets for the control of viral infection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping