biostudies-literatureHu LNational Key R&D Program of ChinaGuangdong Basic and Applied Basic Research FoundationBasic and Applied Basic Research Foundation of Guangdong ProvinceNational Natural Science Foundation of ChinaNational Key Research and Development Program of ChinaScience and Technology Project of Guangzhou Citye10597https://www.ebi.ac.uk/biostudies/studies/S-EPMC12752648biostudies-literatureUnknown12(48)Viral receptors are essential host factors that determine the tropism of oncolytic viruses, and contribute to their selective targeting of cancer cells. In this study, a membrane protein-targeted CRISPR-Cas9 screen is conducted and identify transmembrane protein adipocyte-associated 1 (TPRA1) as a novel receptor for oncolytic virus M1(OVM), a promising oncolytic virus currently under clinical investigation. Mechanistically, TPRA1 facilitates OVM infection by promoting both viral attachment and internalization. Extracellular region of TPRA1 directly binds OVM particles via glycosylation, while its cytoplasmic tail mediates virus endocytosis, collectively enabling efficient viral entry and cancer cell lysis. Importantly, TPRA1 expression in cell lines, mouse models, and patient-derived tumorAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Identification of TPRA1 as a Novel Receptor and Predictive Biomarker for Oncolytic Virus M1.PMC127526482023A03J02002022B151502005682204447823732852021YFA0909800824733242024A1515010317Zhang GYang JYin WZhang JFan ZSong DCai JYi SLin XLin YZeng YLiu YLiu ZHuang SHu CHu JLiang JHu LZhu WYan GfalseIdentification of TPRA1 as a Novel Receptor and Predictive Biomarker for Oncolytic Virus M1.Viral receptors are essential host factors that determine the tropism of oncolytic viruses, and contribute to their selective targeting of cancer cells. In this study, a membrane protein-targeted CRISPR-Cas9 screen is conducted and identify transmembrane protein adipocyte-associated 1 (TPRA1) as a novel receptor for oncolytic virus M1(OVM), a promising oncolytic virus currently under clinical investigation. Mechanistically, TPRA1 facilitates OVM infection by promoting both viral attachment and internalization. Extracellular region of TPRA1 directly binds OVM particles via glycosylation, while its cytoplasmic tail mediates virus endocytosis, collectively enabling efficient viral entry and cancer cell lysis. Importantly, TPRA1 expression in cell lines, mouse models, and patient-derived tumor2025-01-01T00:00:00Z2025 Dec2026-07-15T13:51:53.894Z2026-07-05T03:11:30.503ZS-EPMC127526484105353610.1002/advs.202510597