Background: In the tolerogenic liver, inadequate or ineffective interferon signaling fails to clear chronic HBV infection. Lambda IFNs (IFNL) bind the interferon lambda receptor-1 (IFNLR1) which dimerizes with IL10RB to induce transcription of antiviral interferon-stimulated genes (ISG). IFNLR1 is expressed on hepatocytes, but low expression may limit the strength and antiviral efficacy of IFNL signaling. Three IFNLR1 transcriptional variants are detected in hepatocytes whose role in regulation of IFNL signaling is unclear: a full-length and signaling-capable form (isoform 1), a form that lacks a portion of the intracellular JAK1 binding domain (isoform 2), and a secreted form (isoform 3), the latter two predicted to be signaling defective. We hypothesized that altering expression of IFNLR1 isoforms would differentially impact the hepatocellular response to IFNLs and HBV replication.
Methods: Induced pluripotent stem-cell derived hepatocytes (iHeps) engineered to contain FLAG-tagged, doxycycline-inducible IFNLR1 isoform constructs were HBV-infected then treated with IFNL3 followed by assessment of gene expression, HBV replication, and cellular viability.
Results: Minimal overexpression of IFNLR1 isoform 1 markedly augmented ISG expression, induced de novo proinflammatory gene expression, and enhanced inhibition of HBV replication after IFNL treatment without adversely affecting cell viability. In contrast, overexpression of IFNLR1 isoform 2 or 3 partially augmented IFNL-induced ISG expression but did not support proinflammatory gene expression and minimally impacted HBV replication.
Conclusions: IFNLR1 isoforms differentially influence IFNL-induced gene expression and HBV replication in hepatocytes. Regulated IFNLR1 expression in vivo could limit the capacity of this pathway to counteract HBV replication.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10872352 | PMC |
| http://dx.doi.org/10.1016/j.antiviral.2023.105779 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Environmental exposure to single and combined ZnO and TiO nanoparticles: Implications for rainbow trout gill immune functions and microbiota.
Chemosphere
January 2025
Research Unit in Environmental and Evolutionary Biology (URBE), Institute of Life Earth and Environment, University of Namur, 61 Rue de Bruxelles, B-5000, Namur, Belgium.
ZnO and TiO nanoparticles (NPs) are widely employed for their antibacterial properties, but their potential environmental impact is raising concerns. This study aimed to assess their single and combined effects at environmentally relevant concentrations (210 μg L) on rainbow trout (Oncorhynchus mykiss) gills microbiota and immune functions. 16S rRNA gene sequencing performed after 5 and 28 days of exposure suggests that TiO NPs had a more immediate impact on bacterial diversity, while prolonged exposure to the mixture altered community composition.
View Article and Find Full Text PDFPotential roles of mitochondrial carrier proteins in plant responses to abiotic stress.
J Exp Bot
January 2025
National Institute of Science and Technology on Plant Physiology under Stress Conditions, Departamento de Biologia Vegetal, Universidade Federal de Viçosa, Viçosa 36570-900, Minas Gerais, Brazil.
The transport of metabolites across the inner mitochondrial membrane (IMM) is crucial for maintaining energy balance and efficient distribution of metabolic intermediates between cellular compartments. Under abiotic stress, mitochondrial function becomes particularly critical, activating complex signaling pathways essential for plant stress responses. These pathways modulate stress-responsive gene expression, influencing key physiological processes such as cell respiration and senescence, helping plants adapt to stress.
View Article and Find Full Text PDFMina53 catalyzes arginine demethylation of p53 to promote tumor growth.
Cell Rep
January 2025
Ministry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang Provincial Key Laboratory of Pancreatic Disease, School of Medicine, Zhejiang University, Hangzhou, China; Cancer Center, Zhejiang University, Hangzhou, China. Electronic address:
Arginine methylation is a common post-translational modification that plays critical roles in many biological processes. However, the existence of arginine demethylases that remove the modification has not been fully established. Here, we report that Myc-induced nuclear antigen 53 (Mina53), a member of the jumonji C (JmjC) protein family, is an arginine demethylase.
View Article and Find Full Text PDFProgenitor effect in the spleen drives early recovery via universal hematopoietic cell inflation.
Cell Rep
January 2025
Division of Cell Regulation, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Cell Engineering, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Laboratory for Stem Cell Therapy, Faculty of Medicine, Tsukuba University, Ibaraki, Japan. Electronic address:
Hematopoietic stem cells (HSCs) possess the capacity to regenerate the entire hematopoietic system. However, the precise HSC dynamics in the early post-transplantation phase remain an enigma. Clinically, the initial hematopoiesis in the post-transplantation period is critical, necessitating strategies to accelerate hematopoietic recovery.
View Article and Find Full Text PDFIntegrated metabolomic and transcriptomic strategies to reveal adaptive mechanisms in barley plant during germination stage under waterlogging stress.
J Plant Res
January 2025
College of Marine and Biological Engineering, Yancheng Institute of Technology, Yancheng, 224002, Jiangsu, China.
Barley (Hordeum vulgare L.) is an important cereal crop used in animal feed, beer brewing, and food production. Waterlogging stress is one of the prominent abiotic stresses that has a significant impact on the yield and quality of barley.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!