Plscr1 inhibits murine norovirus entry
- 1University of Texas Southwestern Medical Center
Abstract
Noroviruses are a leading cause of gastroenteritis worldwide, yet host factors that restrict norovirus replication are not well understood. By mining both CRISPR activation and CRISPR knockout genome-wide screens, we identified the interferon-stimulated gene Plscr1 as a restriction factor for murine norovirus (MNV). Plscr1 inhibits the fusion of enveloped viruses with endocytic membranes, making its antiviral activity against the nonenveloped MNV surprising. Here, we demonstrate that Plscr1 is both necessary and sufficient to restrict MNV infection in vitro and contributes to the control of colonic infection in mice. Mechanistically, we determined that Plscr1 inhibits MNV entry at a post-attachment step. A single amino acid substitution in the minor capsid protein VP2 confers resistance to Plscr1. Because VP2 delivers viral RNA by puncturing endocytic membranes during calicivirus entry, these findings implicate a late entry step targeted by Plscr1. Our results expand the antiviral activity of PLSCR1 to a nonenveloped virus and identify an unexpected point of convergence between enveloped- and non-enveloped-virus entry pathways.
Related
- Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1-derived exopolysaccharide suppresses murine norovirus replication by modulating innate immune response
- Evaluation of Human Norovirus Replication in Salivary Gland Cells
- Deep learning-based predictions and analysis of Norovirus dynamics using a fractional-order mathematical model
- NoroScope: Exploring the Mutational Landscape of the Human Norovirus Capsid Protein with Context-Aware Machine Learning
- Prevalence and genotype distribution of norovirus and rotavirus among children under five with diarrheal infection in lower-middle-income countries after Rotavirus vaccine introduction: A systematic review and meta-analysis
BibTeX
@misc{baggett2026plscr1,
title = {{Plscr1 inhibits murine norovirus entry}},
author = {N. S. Baggett and L. R. Pierce and R. C. Orchard},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.752154},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752154v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Plscr1 inhibits murine norovirus entry
AU - N. S. Baggett
AU - L. R. Pierce
AU - R. C. Orchard
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.752154
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.752154v1
AB - Noroviruses are a leading cause of gastroenteritis worldwide, yet host factors that restrict norovirus replication are not well understood. By mining both CRISPR activation and CRISPR knockout genome-wide screens, we identified the interferon-stimulated gene Plscr1 as a restriction factor for murine norovirus (MNV). Plscr1 inhibits the fusion of enveloped viruses with endocytic membranes, making its antiviral activity against the nonenveloped MNV surprising. Here, we demonstrate that Plscr1 is both necessary and sufficient to restrict MNV infection in vitro and contributes to the control of colonic infection in mice. Mechanistically, we determined that Plscr1 inhibits MNV entry at a post-attachment step. A single amino acid substitution in the minor capsid protein VP2 confers resistance to Plscr1. Because VP2 delivers viral RNA by puncturing endocytic membranes during calicivirus entry, these findings implicate a late entry step targeted by Plscr1. Our results expand the antiviral activity of PLSCR1 to a nonenveloped virus and identify an unexpected point of convergence between enveloped- and non-enveloped-virus entry pathways.
ER -