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Antiviral activity of bone morphogenetic proteins and activins
- Publication Year :
- 2019
- Publisher :
- Springer Nature, 2019.
-
Abstract
- Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic. HCV blunted induction of hepcidin expression by BMP6, probably via tumour necrosis factor (TNF)-mediated downregulation of the BMP co-receptor haemojuvelin. In HCV-infected patients, disruption of the BMP6/hepcidin axis and genetic variation associated with the BMP/SMAD pathway predicted the outcome of infection, suggesting that BMP/SMAD activity influences antiviral immunity. Correspondingly, BMP6 regulated a gene repertoire reminiscent of type I interferon (IFN) signalling, including upregulating interferon regulatory factors (IRFs) and downregulating an inhibitor of IFN signalling, USP18. Moreover, in BMP-stimulated cells, SMAD1 occupied loci across the genome, similar to those bound by IRF1 in IFN-stimulated cells. Functionally, BMP6 enhanced the transcriptional and antiviral response to IFN, but BMP6 and related activin proteins also potently blocked HCV replication independently of IFN. Furthermore, BMP6 and activin A suppressed growth of HBV in cell culture, and activin A inhibited Zika virus replication alone and in combination with IFN. The data establish an unappreciated important role for BMPs and activins in cellular antiviral immunity, which acts independently of, and modulates, IFN.
- Subjects :
- Microbiology (medical)
animal structures
Bone Morphogenetic Protein 6
Immunology
SMAD
Hepacivirus
Bone morphogenetic protein
Virus Replication
Applied Microbiology and Biotechnology
Microbiology
Antiviral Agents
Article
Smad1 Protein
03 medical and health sciences
Downregulation and upregulation
Hepcidins
Interferon
Hepcidin
Endopeptidases
Genetics
medicine
Humans
Cells, Cultured
030304 developmental biology
0303 health sciences
biology
030306 microbiology
Interferon-alpha
Cell Biology
Zika Virus
Hepatitis C
Activins
Bone morphogenetic protein 6
IRF1
Gene Expression Regulation
Interferon Regulatory Factors
embryonic structures
Cancer research
biology.protein
RNA, Viral
Ubiquitin Thiolesterase
Interferon regulatory factors
medicine.drug
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20585276
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b3712a070ea9fbbc58aeacfc182a4dd1