State Key Laboratory of Veterinary Biotechnology, Heilongjiang Provincial Key Laboratory of Laboratory Animal and Comparative Medicine, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Viruses. 2023 Apr 5;15(4):920. doi: 10.3390/v15040920.
Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane protein enriched on the surface of some cells, including melanoma, glioblastoma, and macrophages. GPNMB has been reported to have multifaceted roles, such as facilitating cell-cell adhesion and migration, stimulating kinase signaling, and regulating inflammation. Porcine reproductive and respiratory syndrome virus (PRRSV) is the leading cause of severe economic loss in the swine industry worldwide. In this study, the role of GPNMB was investigated in porcine alveolar macrophages during PRRSV infection. We observed that GPNMB expression was markedly reduced in PRRSV-infected cells. The inhibition of GPNMB by specific small interfering RNA led to an enhancement in virus yields, and GPNMB overexpression decreased PRRSV replication. Further studies revealed that the overexpression of GPNMB could induce the accumulation of autophagosome through inhibiting autophagosome-lysosome fusion. Using a specific inhibitor, we confirmed that the inhibition of autophagosome-lysosome fusion significantly inhibited viral replication. Taken together, our data demonstrate that GPNMB inhibits PRRSV replication by inhibiting the autophagosome-lysosome fusion and provides a novel therapeutic target for virus infection.
糖蛋白非转移性黑色素瘤蛋白 B（GPNMB）是一种富含于某些细胞表面的跨膜蛋白，包括黑色素瘤、神经胶质瘤和巨噬细胞。已有报道称，GPNMB 具有多方面的作用，如促进细胞-细胞黏附和迁移、刺激激酶信号转导以及调节炎症。猪繁殖与呼吸综合征病毒（PRRSV）是全球养猪业造成严重经济损失的主要原因。在本研究中，研究了 GPNMB 在 PRRSV 感染猪肺泡巨噬细胞中的作用。我们观察到，PRRSV 感染细胞中的 GPNMB 表达明显降低。特异性小干扰 RNA 抑制 GPNMB 会导致病毒产量增加，而过表达 GPNMB 会降低 PRRSV 的复制。进一步的研究表明，过表达 GPNMB 可通过抑制自噬体-溶酶体融合来诱导自噬体的积累。使用特异性抑制剂证实，抑制自噬体-溶酶体融合可显著抑制病毒复制。综上所述，我们的数据表明，GPNMB 通过抑制自噬体-溶酶体融合来抑制 PRRSV 的复制，并为病毒感染提供了一个新的治疗靶点。
