牛冠状病毒通过膜融合和网格蛋白、小窝蛋白介导的内吞作用、大吞噬作用进入PBIEC
Bovine coronavirus enters PBIECs via membrane fusion and clathrin-, caveolin-mediated endocytosis, macropinocytosis.
摘要(中文译文)
牛冠状病毒（BCoV）是一种重要的病原体，对呼吸道和肠道具有双重嗜性，可导致成年牛冬季痢疾、犊牛腹泻和呼吸道感染，从而给全球养牛业造成相当大的经济损失。我们此前的研究表明，BCoV通过膜融合和网格蛋白介导的内吞（CME）进入敏感的HRT-18细胞。然而，BCoV进入宿主细胞的确切机制仍未完全阐明，尤其是在原代牛肠上皮细胞（PBIECs）中。重要的是，作为来源于天然宿主的原代细胞，PBIECs比HRT-18细胞系更能再现感染微环境。在本研究中，采用化学抑制剂、RNA干扰和荧光标记的BCoV颗粒来界定不同的进入途径。我们的数据表明，BCoV通过膜融合和三种不同的内吞途径进入PBIECs，包括CME、小窝蛋白介导的内吞（CavME）和巨胞饮。动力蛋白、微管、组织蛋白酶和酸性环境对于介导内吞进入至关重要，而胆固醇和TMPRSS2在此过程中并非必需。此外，靶向干扰Rab5、Rab7和Rab11可抑制BCoV进入PBIECs。与此一致，通过共聚焦显微镜观察到荧光标记的BCoV与Rab5、Rab7和Rab11共定位，表明这些Rab GTP酶参与BCoV进入PBIECs。这些发现阐明了BCoV的进入机制，并为更全面地理解BCoV生命周期提供了新的视角。
Abstract
Bovine coronavirus (BCoV) is an important pathogen that exhibits dual tropism for the respiratory and intestinal tracts, causing winter dysentery in adult cattle, diarrhea and respiratory infections in calves, thus imposing considerable economic losses on the global cattle industry. Our previous studies demonstrated that BCoV gains entry into susceptible HRT-18 cells through membrane fusion and clathrin-mediated endocytosis (CME). However, the precise mechanisms by which BCoV enters host cells remain incompletely elucidated, particularly in primary bovine intestinal epithelial cells (PBIECs). Importantly, as primary cells derived from the natural host, PBIECs more closely recapitulate the in infection microenvironment than HRT-18 cell lines. In the present study, chemical inhibitors, RNA interference, and fluorescently labeled BCoV particles were used to define distinct entry pathways. Our data demonstrated that BCoV enters PBIECs via membrane fusion and three distinct endocytic pathways, including CME, caveolin-mediated endocytosis (CavME), and macropinocytosis. Dynamin, microtubules, cathepsins, and an acidic environment are essential for mediating endocytic entry, whereas cholesterol and TMPRSS2 are dispensable for this process. Furthermore, targeted interference with Rab5, Rab7, and Rab11 suppressed BCoV entry into PBIECs. Consistently, co-localization of fluorescently labeled BCoV with Rab5, Rab7, and Rab11 was observed by confocal microscopy, indicating that these Rab GTPases are involved in BCoV entry into PBIECs. These findings elucidate the entry mechanisms of BCoV and provide novel perspectives to enhance a more comprehensive understanding of the BCoV life cycle.
如何引用
AMA
Chen Chen, Nannan Su, Long Zhao, Ning Li, Zhongyuan Ma, Bihao Luo, et al. Bovine coronavirus enters PBIECs via membrane fusion and clathrin-, caveolin-mediated endocytosis, macropinocytosis.. Virulence. 2026; doi:10.1080/21505594.2026.2691344.
APA
Chen Chen, Nannan Su, Long Zhao, Ning Li, Zhongyuan Ma, Bihao Luo, et al (2026). Bovine coronavirus enters PBIECs via membrane fusion and clathrin-, caveolin-mediated endocytosis, macropinocytosis.. Virulence. https://doi.org/10.1080/21505594.2026.2691344
GB/T 7714
Chen Chen, Nannan Su, Long Zhao, Ning Li, Zhongyuan Ma, Bihao Luo, et al. Bovine coronavirus enters PBIECs via membrane fusion and clathrin-, caveolin-mediated endocytosis, macropinocytosis.[J]. Virulence, 2026 doi:10.1080/21505594.2026.2691344.
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