Zhou Junyi, Zhang Huimin, Wu Gaochun, Zhang Yinghao, Aweya Jude Juventus, Tayyab Muhammad, Zhu Jinghua, Zhang Yueling, Yao Defu
Institute of Marine Sciences and Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou, China.
Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
mBio. 2025 Mar 12;16(3):e0378724. doi: 10.1128/mbio.03787-24. Epub 2025 Feb 18.
White spot syndrome virus (WSSV) is a debilitating viral pathogen that poses a significant threat to the global crustacean farming industry. It has a wide host tropism because it uses several receptors to facilitate its attachment and entry. Thus far, not all the receptors have been identified. Here, we employed a BioID-based screening method to identify the Na-K-ATPase alpha subunit (ATP1A) as a potential receptor in . Although during the early stages of WSSV infectionATP1A was induced and underwent oligomerization, clustering, and internalization, knockdown of ATP1A inhibited viral entry and replication. ATP1A interacted with the WSSV envelope protein VP28 through its multiple extracellular regions, whereas synthetic ATP1A extracellular region peptides blocked WSSV entry and replication. We showed that ATP1A did not affect WSSV attachment but facilitated internalization via caveolin-mediated endocytosis and macropinocytosis. These findings provide a robust receptor screening approach that identified ATP1A as an entry receptor for WSSV, presenting a novel target for the development of anti-WSSV therapeutics.
Cell surface receptors are crucial for mediating virus entry into host cells. Identification and characterization of virus receptors are fundamental yet challenging aspects of virology research. In this study, a BioID-based screening method was employed to identify the Na-K-ATPase alpha subunit (ATP1A) as a potential receptor for white spot syndrome virus (WSSV) in the shrimp . We demonstrated that ATP1A interacted with the WSSV envelope protein VP28 via its multiple extracellular regions, thereby promoting viral internalization through caveolin-mediated endocytosis and macropinocytosis. Importantly, compared with previously identified WSSV receptors such as β-integrin, glucose transporter 1 (Glut1), and polymeric immunoglobulin receptor (pIgR), ATP1A demonstrated significantly enhanced viral entry, indicating that ATP1A is a crucial entry receptor of WSSV. This study not only presents a robust approach for screening virus receptors but also identifies ATP1A as a promising target for the development of anti-WSSV therapeutics.
白斑综合征病毒（WSSV）是一种致病性病毒病原体，对全球甲壳类养殖产业构成重大威胁。它具有广泛的宿主嗜性，因为它利用多种受体来促进其附着和进入。到目前为止，并非所有受体都已被鉴定出来。在这里，我们采用了一种基于生物素识别技术（BioID）的筛选方法，鉴定出钠钾ATP酶α亚基（ATP1A）作为（虾中）一种潜在的受体。尽管在WSSV感染早期ATP1A被诱导并发生寡聚化、聚集和内化，但ATP1A的敲低抑制了病毒的进入和复制。ATP1A通过其多个细胞外区域与WSSV包膜蛋白VP28相互作用，而合成的ATP1A细胞外区域肽段可阻断WSSV的进入和复制。我们发现ATP1A不影响WSSV的附着，但通过小窝蛋白介导的内吞作用和巨胞饮作用促进内化。这些发现提供了一种强大的受体筛选方法，该方法鉴定出ATP1A作为WSSV的进入受体，为抗WSSV治疗药物的开发提供了一个新的靶点。
细胞表面受体对于介导病毒进入宿主细胞至关重要。病毒受体的鉴定和表征是病毒学研究的基本但具有挑战性的方面。在本研究中，采用了一种基于生物素识别技术（BioID）的筛选方法，鉴定出钠钾ATP酶α亚基（ATP1A）作为虾中白斑综合征病毒（WSSV）的一种潜在受体。我们证明，ATP1A通过其多个细胞外区域与WSSV包膜蛋白VP28相互作用，从而通过小窝蛋白介导的内吞作用和巨胞饮作用促进病毒内化。重要的是，与先前鉴定的WSSV受体如β-整合素、葡萄糖转运蛋白1（Glut1）和聚合免疫球蛋白受体（pIgR）相比，ATP1A显示出显著增强的病毒进入能力，表明ATP1A是WSSV的关键进入受体。本研究不仅提供了一种强大的病毒受体筛选方法，还鉴定出ATP1A作为抗WSSV治疗药物开发的一个有前景的靶点。
