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Updated: Jul 17, 2026
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Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes
Published on: May 23, 2025
Genome-wide CRISPR screen reveals PEX11B as a host restriction factor against ORFV through membrane fluidity
Xiaoran Gao1, Jinyang Hao1, Sha Lu1,2
1The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, P.R.China.
Plos Pathogens
|July 15, 2026
Summary
Researchers discovered PEX11B, a peroxisomal protein, acts as a key antiviral defense against orf virus (ORFV). Deleting PEX11B in sheep cells increased viral infection by altering cell membranes and disrupting peroxisome function.
Area of Science:
- Virology
- Cell Biology
- Genetics
Background:
- Cellular restriction factors are crucial for innate antiviral immunity.
- Understanding host-pathogen interactions requires identifying novel restriction factors.
Purpose of the Study:
- To identify novel ovine restriction factors against orf virus (ORFV) using a genome-wide CRISPR knockout library.
- To elucidate the antiviral mechanism of identified restriction factors.
Main Methods:
- Construction of the first ovine genome-wide CRISPR knockout library in sheep testis (OA3.Ts) cells.
- CRISPR screening to identify genes conferring susceptibility to ORFV infection.
- Cellular and molecular analyses to investigate the role of PEX11B in host-virus interactions.
Main Results:
- Identification of PEX11B, a peroxisomal membrane protein, as a potent ORFV restriction factor.
- PEX11B knockout cells exhibited increased susceptibility to ORFV, with severe cytopathic effects including syncytia formation.
- PEX11B deficiency disrupted peroxisomal integrity and lipid metabolism, increasing plasma membrane fluidity and promoting viral entry.
Conclusions:
- PEX11B possesses a novel antiviral function by maintaining peroxisomal integrity and regulating membrane properties.
- Peroxisomal regulation is critical for host antiviral defense against viruses like ORFV.
- This study highlights PEX11B as a potential target for antiviral strategies.
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