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Bmp8a is an essential positive regulator of antiviral immunity in zebrafish

Shenjie Zhong, Haoyi Li, Yun-Sheng Wang, Ying Wang, Guangdong Ji, Hongyan Li, Shicui Zhang, Zhenhui Liu

2021Communications Biology18 citationsDOIOpen Access PDF

Abstract

Abstract Bone morphogenetic protein (BMP) is a kind of classical multi-functional growth factor that plays a vital role in the formation and maintenance of bone, cartilage, muscle, blood vessels, and the regulation of adipogenesis and thermogenesis. However, understanding of the role of BMPs in antiviral immunity is still limited. Here we demonstrate that Bmp8a is a newly-identified positive regulator for antiviral immune responses. The bmp8a −/− zebrafish, when infected with viruses, show reduced antiviral immunity and increased viral load and mortality. We also show for the first time that Bmp8a interacts with Alk6a, which promotes the phosphorylation of Tbk1 and Irf3 through p38 MAPK pathway, and induces the production of type I interferons (IFNs) in response to viral infection. Our study uncovers a previously unrecognized role of Bmp8a in regulation of antiviral immune responses and provides a target for controlling viral infection.

Topics & Concepts

IRF3BiologyZebrafishImmune systemRegulatorImmunityCell biologyTANK-binding kinase 1PhosphorylationAdipogenesisMAPK/ERK pathwayVirologyImmunologyInnate immune systemGeneticsMesenchymal stem cellGeneMAP kinase kinase kinaseinterferon and immune responsesCytokine Signaling Pathways and InteractionsCancer-related molecular mechanisms research