{ "abstract": "Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a bat-originated alphacoronavirus that causes devastating enteric disease in neonatal piglets and possesses significant potential for cross-species transmission. While the early stages of the coronavirus life cycle have been extensively characterized, the host factors indispensable for virion assembly and subsequent export remain largely enigmatic. Here, by performing a genome-wide CRISPR-Cas9 knockout screen using a recombinant icSADS-CoV-GFP reporter virus, we identified the small GTPase Rab10 as a critical host dependency factor for SADS-CoV infection. Viral life cycle analysis revealed that Rab10 is not required for viral attachment, entry, or initial genome replication, but is essential for the virion transport and non-lytic egress. Rab10 deficiency markedly reduced the extracellular release of viral RNA, viral proteins, and infectious progeny, as well as the secretion of SADS-CoV virus-like particles. Confocal imaging showed that Rab10 and viral protein-positive intracellular structures were associated with LMAN1, TGN46, and LAMP1 positive compartments. These findings support a model in which Rab10 coordinates a virus-containing vesicles trafficking pathway associated with ERGIC-TGN-lysosome compartments. Mechanistically, Rab10 facilitates the loading of the viral envelope (E) protein into transport vesicles derived from the ERGIC. Rab10 associates with the SADS-CoV E protein, and mapping analyses implicated the C-terminal PDZ-binding motif, particularly residue V75, in efficient Rab10 association and viral release. Collectively, our findings identify Rab10 as a host regulator of SADS-CoV non-lytic egress and highlight the E-Rab10 interaction and the vesicular trafficking machinery as a potential target for developing antiviral strategies. Author summary: Coronaviruses, including the emerging SADS-CoV, are notorious for their ability to cross species barriers and cause severe diseases. While it is well-established how these viruses enter cells and replicate their genetic material, the mechanisms of non-lytic egress, which allows progeny virions to exit the host cell and infect neighboring cells without compromising host cell viability, remain poorly understood. Here, we employed a genome-wide CRISPR-Cas9 screening approach and identified Rab10 as a pivotal host factor regulating SADS-CoV infection. We discovered that while Rab10 is dispensable for viral entry and assembly, but instead promotes a later stage of virus trafficking and non-lytic release. This guide service is triggered by an association between Rab10 and the viral E protein. By identifying the specific amino acid V75 as viral site that interacts with Rab10, we have uncovered a critical host-pathogen interface within the SADS-CoV life cycle. These findings reveal how SADS-CoV uses host membrane trafficking machinery for efficient egress and identify the E–Rab10 interaction as a potential target for future antiviral development.", "abstract_shown": true, "affiliations": [ "State Key Laboratory of Animal Disease Control and Prevention, Chinese Academy of Agricultural Sciences Harbin Veterinary Research Institute, Harbin, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 14, "authors": [ { "affs": [ 0 ], "name": "Liaoyuan Zhang" }, { "name": "Jiyu Zhang" }, { "name": "Mei Xue" }, { "name": "Mengyu Liu" }, { "name": "Xinwei Sun" }, { "name": "Dakai Liu" }, { "name": "Miaomiao Zeng" }, { "name": "Gengting Gu" }, { "name": "Hongyan Shi" }, { "name": "Xin Zhang" }, { "name": "Jianfei Chen" }, { "name": "Zhaoyang Ji" }, { "name": "Da Shi" }, { "name": "Li Feng" } ], "bibtex": "https://research.draconitic.com/paper/5110pm79hgw45.bib", "cited_by": 0, "doi": "10.1371/journal.ppat.1014569", "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014569", "id": "5110pm79hgw45", "issns": [ "1553-7374" ], "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014569", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "1307|Cellular transport and secretion" ], [ "plos", "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/Small interfering RNA" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Protein transport" ], [ "plos", "/Biology and life sciences/Cell biology/Cell processes/Protein transport" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular structures and organelles/Vesicles" ], [ "plos", "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Small interfering RNA" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Viral pathogens/Coronaviruses" ], [ "plos", "/Biology and life sciences/Microbiology/Virology/Viral replication" ], [ "plos", "/Biology and life sciences/Microbiology/Virology/Viral structure/Virions" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/RNA viruses/Coronaviruses" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Viral pathogens/Coronaviruses" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Viral pathogens/Coronaviruses" ], [ "plos", "/Research and analysis methods/Biological cultures/Cell cultures/Cultured tumor cells/HeLa cells" ], [ "plos", "/Research and analysis methods/Biological cultures/Cell lines/HeLa cells" ], [ "plos", "/Research and analysis methods/Specimen preparation and treatment/Staining/Nuclear staining/DAPI staining" ] ], "openalex": "W7204960590", "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014569&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-01", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/5110pm79hgw45.ris", "sources": [ { "first_seen": "2026-10-30T12:18:02Z", "native_id": "10.1371/journal.ppat.1014569", "source": "plos", "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014569" } ], "subjects": [ { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:microbiology", "subfield": "microbiology" } ], "title": "Rab10 coordinates SADS-CoV non-lytic egress through the ERGIC-TGN-lysosome trafficking pathway", "title_text": "Rab10 coordinates SADS-CoV non-lytic egress through the ERGIC-TGN-lysosome trafficking pathway", "type": "peer-reviewed", "updated_at": "2026-10-30T12:18:02Z", "url": "https://research.draconitic.com/paper/5110pm79hgw45", "venue": "PLOS Pathogens", "versions": [] }