{"id":236,"title":"Nectin-4 mediates rubella virus entry in airway and placental cells","title_zh":"Nectin-4是风疹病毒侵入气道与胎盘细胞的功能性受体","url":"https://pubmed.ncbi.nlm.nih.gov/42983085","doi":"10.1038/s41586-026-11248-2","pmid":"42983085","journal":"Nature","kind":"paper","lang":"en","published_at":"2026-11-04T00:00:00+00:00","fetched_at":"2026-11-08T03:44:00+00:00","authors":["Mori Y","Sakata M","Nakatsu Y","Hori T","Ino Y","Suzuki S","Nishi M","Kawase M","Kakizaki M","Nagai M","Fukano K","Aizaki H","Hayashi H","Murayama K","Kodama EN","Taguwa S","Okura T","Takahashi T","Kamitani W","Shirato K","Isogawa M","Kimura Y","Kaji H","Matsuura Y","Ryo A"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":6.0,"hits":["maternal-fetal interface","placental","trophoblast"]},{"slug":"ethics-policy","score":1.0,"hits":["crispr"]},{"slug":"omics-methods","score":1.0,"hits":["proteomics"]}],"topic_score":6.0,"preference_score":0.0,"preference_labels":[],"llm_score":72.0,"final_score":84.0,"score_dims":{"novelty":82,"rigor":88,"impact":70,"relevance":45,"translation":55},"recommend_reason":"Nature级别的受体鉴定工作，机制链条完整，对理解孕期风疹病毒母胎界面感染与呼吸道传播有重要价值；但研究对象为病毒侵入而非胚胎/内膜本身，与辅助生殖核心范畴相关性有限。","keywords":["风疹病毒","nectin-4","病毒受体","合体滋养层","母胎界面","先天性风疹综合征"],"selected":1,"story_id":86,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-uterus-pregnancy","source_name":"PubMed · 内膜/植入/早孕","source_tier":1,"mention_count":3,"has_interpretation":false,"journal_key":"nature","journal_tier":"cns","journal_if":50.5,"is_mock":false,"summary_zh":"研究采用邻近生物素标记蛋白质组学结合CRISPR-Cas9验证，鉴定nectin-4为风疹病毒（RuV）的功能性侵入受体。异位表达nectin-4使非允许细胞易感，阻断或基因敲除则降低感染；机制上nectin-4直接结合RuV包膜糖蛋白异二聚体，在钙依赖性初始附着后介导受体依赖性内吞。极化气道上皮模型中nectin-4介导基底侧侵入并支持顶端子代释放，为呼吸道传播提供分子机制；胎盘模型中nectin-4高表达于合体滋养层，促进母胎界面感染，但其他滋养层细胞感染存在非依赖途径。","summary":"Rubella virus (RuV) causes rubella and, when acquired during pregnancy, congenital rubella syndrome1. Despite its clinical significance, the cellular entry mechanism of RuV remains poorly characterized, owing to limited identification of host receptors2, which hinders pathogenesis research and therapeutic development. Here, using proximity biotin labelling-based proteomics coupled with CRISPR-Cas9 validation, we identify nectin-4 as a functional RuV entry receptor. Ectopic expression of nectin-4 conferred susceptibility to RuV in non-permissive cells, whereas blocking or genetic ablation of nectin-4 reduced infection, results that demonstrate that nectin-4 is a major entry factor. Mechanistically, nectin-4 directly interacts with the RuV envelope glycoprotein heterodimer and facilitates receptor-mediated endocytosis following initial calcium-dependent viral attachment to cellular lipids. In polarized airway epithelial models, nectin-4 mediates basolateral entry of RuV and supports apical progeny release, a finding that provides a molecular mechanism for respiratory transmission. In placental models, nectin-4 is highly expressed on syncytiotrophoblasts and facilitates infection at the maternal-fetal interface, although additional nectin-4-independent pathways contribute to infection of other trophoblast populations. Together, these data establish nectin-4 as a key factor for respiratory transmission and early placental infection of RuV and highlight it as a promising therapeutic target for the prevention of rubella and related diseases.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}