Knockdown of fibrillarin reveals cell- and virus- dependent restriction of henipavirus replication and enhanced antiviral immune signalling

Sathiqu, R. M.; Rootes, C.; Brice, A. M.; Caputo, A. T.; Williams, S. M.; Rodrigues, C. H. M.; Farr, R. J.; Alexander, M.; Stewart, C.

doi:10.64898/2026.11.02.763686

bioRxiv · 10.64898/2026.11.02.763686

Knockdown of fibrillarin reveals cell- and virus- dependent restriction of henipavirus replication and enhanced antiviral immune signalling

Sathiqu, R. M.·Rootes, C.·Brice, A. M.·Caputo, A. T.·Williams, S. M.·Rodrigues, C. H. M.·Farr, R. J.·Alexander, M.·Stewart, C.

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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.

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Sathiqu, R. M., Rootes, C., Brice, A. M., Caputo, A. T., Williams, S. M., Rodrigues, C. H. M., Farr, R. J., Alexander, M., Stewart, C.. 2026-11-03. Knockdown of fibrillarin reveals cell- and virus- dependent restriction of henipavirus replication and enhanced antiviral immune signalling. https://doi.org/10.64898/2026.11.02.763686

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