Knockdown of fibrillarin reveals cell- and virus- dependent restriction of henipavirus replication and enhanced antiviral immune signalling
- 1Commonwealth Scientific and Industrial Research Organisation
Abstract
The henipavirus genus includes several highly pathogenic zoonotic viruses that lack medical countermeasures. The 2-O-methyltransferase fibrillarin (FBL) has been identified by genome-wide functional genomics studies as a henipavirus pro-viral factor. While FBL is a potential target for host-directed antiviral therapeutics, its impact on henipavirus replication in cell types relevant to henipavirus disease has not been explored. Here we demonstrate that depleting cellular FBL using short interfering RNAs (siRNAs) has varying impacts on henipavirus replication, depending on cell type and virus. FBL depletion in small airway epithelial cells (HSAEC1-KT) significantly impaired viral gene transcription for Hendra virus (HeV) genotypes 1 and 2 (HeV-g1, HeV-g2), and Nipah virus (NiV) Bangladesh strain (NiV-B), but not NiV Malaysia (NiV-M) strain or Cedar virus (CedV). Conversely, reduced FBL expression in bronchial epithelial (NuLi-1) cells, aortic endothelial (Telo HAEC) cells or neuroblastoma (BE(2)-M17) cells did not inhibit HeV-g1 replication. Transcriptomic analyses revealed that impaired virus replication in FBL knockdown cells was associated with enhanced activation of innate immune pathways and robust upregulation of interferon stimulated genes (ISGs). Together, these findings demonstrate a virus- and cell-type dependent impact of FBL on henipavirus replication and support a role for FBL in modulation of the antiviral innate immune response.
Related
- tRNA-derived fragments restrict KSHV lytic replication through miRNA-like repression of host pro-viral signalling networks
- HOXA3 Knockdown Impairs hESC-Derived Thymic Epithelial-like Cell Differentiation and CXCL12-Associated Early T-Lineage Support
- Integrated transcriptomics, metabolomics, and gut microbiome analysis reveals the association between Rnf43 knockdown and intestinal epithelial hyperproliferation in HFD/AOM/DSS treated mice
- Design guide for synthetic small regulatory RNAs for high-efficiency gene knockdown in bacteria
- Curcumin-Derived J147 Protects HT22 Cells from Cell Death Under Tunicamycin-Induced Endoplasmic Reticulum Stress with CHOP Suppression Retained After ATP5A Knockdown
BibTeX
@misc{sathiqu2026knockdown,
title = {{Knockdown of fibrillarin reveals cell- and virus- dependent restriction of henipavirus replication and enhanced antiviral immune signalling}},
author = {R. M. Sathiqu and C. Rootes and A. M. Brice and A. T. Caputo and S. M. Williams and C. H. M. Rodrigues and R. J. Farr and M. Alexander and C. Stewart},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.02.763686},
url = {https://www.biorxiv.org/content/10.64898/2026.11.02.763686v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Knockdown of fibrillarin reveals cell- and virus- dependent restriction of henipavirus replication and enhanced antiviral immune signalling
AU - R. M. Sathiqu
AU - C. Rootes
AU - A. M. Brice
AU - A. T. Caputo
AU - S. M. Williams
AU - C. H. M. Rodrigues
AU - R. J. Farr
AU - M. Alexander
AU - C. Stewart
PY - 2026
DA - 2026/11/02
PB - bioRxiv
DO - 10.64898/2026.11.02.763686
UR - https://www.biorxiv.org/content/10.64898/2026.11.02.763686v1
AB - The henipavirus genus includes several highly pathogenic zoonotic viruses that lack medical countermeasures. The 2-O-methyltransferase fibrillarin (FBL) has been identified by genome-wide functional genomics studies as a henipavirus pro-viral factor. While FBL is a potential target for host-directed antiviral therapeutics, its impact on henipavirus replication in cell types relevant to henipavirus disease has not been explored. Here we demonstrate that depleting cellular FBL using short interfering RNAs (siRNAs) has varying impacts on henipavirus replication, depending on cell type and virus. FBL depletion in small airway epithelial cells (HSAEC1-KT) significantly impaired viral gene transcription for Hendra virus (HeV) genotypes 1 and 2 (HeV-g1, HeV-g2), and Nipah virus (NiV) Bangladesh strain (NiV-B), but not NiV Malaysia (NiV-M) strain or Cedar virus (CedV). Conversely, reduced FBL expression in bronchial epithelial (NuLi-1) cells, aortic endothelial (Telo HAEC) cells or neuroblastoma (BE(2)-M17) cells did not inhibit HeV-g1 replication. Transcriptomic analyses revealed that impaired virus replication in FBL knockdown cells was associated with enhanced activation of innate immune pathways and robust upregulation of interferon stimulated genes (ISGs). Together, these findings demonstrate a virus- and cell-type dependent impact of FBL on henipavirus replication and support a role for FBL in modulation of the antiviral innate immune response.
ER -