Genome-wide CRISPR screen reveals PEX11B as a host restriction factor against ORFV through membrane fluidity regulation.

Authors

Xiaoran Gao, Jinyang Hao, Sha Lu, Shida Wang, Yu Sun, Xin Ke, Xia Gao, Yuan Su, Yuze Sun, Yu Tian, Wenyu Yan, Jinliang Wang, Zhong Zheng, Rong Hai, Qianyi Zhang, Jingfei Wang, Wei Hu, Guojun Wang

Published in

PLoS pathogens. Volume 22. Issue 7. Pages e1013767. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Host-pathogen interactions are shaped by cellular restriction factors that direct antiviral defenses. We built the first ovine genome-wide CRISPR knockout library in sheep testis (OA3.Ts) cells, targeting all protein-coding genes. Using this platform, we identified PEX11B, a peroxisomal membrane regulatory protein, as a strong restriction factor against orf virus (ORFV) infection. Removing PEX11B increased viral susceptibility and triggered severe cytopathic effects with membrane fusion and syncytia formation. Mechanistic studies showed that PEX11B knockout harmed peroxisomal integrity and disrupted lipid metabolism. This led to greater plasma membrane fluidity, creating a proviral environment that allowed more viral entry and replication. These results reveal a new antiviral function for PEX11B in blocking viral infection and underscore the importance of peroxisomal regulation in host-virus interactions.

PMID:
42455881
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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