State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China; Mekelle University College of Veterinary Sciences, Mekelle, Tigray, Ethiopia.
Vet Microbiol. 2024 Nov;298:110254. doi: 10.1016/j.vetmic.2024.110254. Epub 2024 Sep 19.
Lumpy skin disease virus (LSDV), a ruminant poxvirus of the Capripoxvirus genus, is the etiologic agent of an economically important cattle disease categorized as a notifiable disease by the World Organization for Animal Health. However, the endocytic pathway and their regulatory molecules have not been characterized for LSDV. In the present study, specific pharmacological inhibitors were used to analyze the mechanism of LSDV entry into Mardin-Darby Bovine Kidney cell (MDBK) and bovine mammary epithelial cell (BMEC). The results showed that LSDV entered MDBK and BMEC cells depends on low-pH conditions and dynamin. However, the inhibitor of caveolae- and clathrin-mediated endocytosis cann't inhibit LSDV entry into MDBK and BMEC cells. Furthermore, treatment with specific inhibitors demonstrated that LSDV entry into MDBK and BMEC cells via macropinocytosis depended on the Na1/H1 exchanger (NHE) but not phosphatidylinositol 3-kinase (PI3K). In addition, results demonstrated that these inhibitors inhibited LSDV entry but did not have effect on LSDV binding. Taken together, our study demonstrated that LSDV enters MDBK and BMEC cells through macropinocytosis pathway in a low-PH- and dynamin-dependent manner while independent on PI3K. Results presented in this study potentially provides insight into the entry mechanisms of LSDV, and it may facilitate the development of therapeutic interventions.
块状皮肤疾病病毒（LSDV）是反刍动物痘病毒属的一种，是一种经济上重要的牛病的病原体，被世界动物卫生组织列为法定报告疾病。然而，LSDV 的内吞途径及其调节分子尚未得到描述。在本研究中，使用特定的药理学抑制剂来分析 LSDV 进入 Mardin-Darby 牛肾细胞（MDBK）和牛乳腺上皮细胞（BMEC）的机制。结果表明，LSDV 进入 MDBK 和 BMEC 细胞依赖于低 pH 条件和胞吞作用。然而，内吞小窝和网格蛋白介导的内吞作用抑制剂不能抑制 LSDV 进入 MDBK 和 BMEC 细胞。此外，用特异性抑制剂处理表明，LSDV 通过胞饮作用进入 MDBK 和 BMEC 细胞依赖于钠氢交换体（NHE）而不是磷脂酰肌醇 3-激酶（PI3K）。此外，结果表明这些抑制剂抑制了 LSDV 的进入，但对 LSDV 的结合没有影响。综上所述，我们的研究表明，LSDV 通过低 pH 和胞吞作用依赖于胞吞作用进入 MDBK 和 BMEC 细胞，而不依赖于 PI3K。本研究结果可能为 LSDV 的进入机制提供了新的认识，并可能有助于开发治疗干预措施。
