Lysosomes are involved in pathogenesis of a variety of neurodegenerative diseases and play a large role in neurodegenerative disorders caused by virus infection. However, whether virus-infected cells or animals can be used as experimental models of neurodegeneration in humans based on virus-related lysosomal dysfunction remain unclear. Porcine hemagglutinating encephalomyelitis virus displays neurotropism in mice, and neural cells are its targets for viral progression. PHEV infection was confirmed to be a risk factor for neurodegenerative diseases in the present. The findings demonstrated for the first time that PHEV infection can lead to lysosome disorders and showed that the specific mechanism of lysosome dysfunction is related to PGRN expression deficiency and indicated similar pathogenesis compared with human neurodegenerative diseases upon PHEV infection. Trehalose can also increase progranulin expression and rescue abnormalities in lysosomal structure in PHEV-infected cells. In conclusion, these results suggest that PHEV probably serve as a disease model for studying the pathogenic mechanisms and prevention of other degenerative diseases.

溶酶体参与多种神经退行性疾病的发病机制，在病毒感染引起的神经退行性疾病中发挥重要作用。然而，病毒感染的细胞或动物是否可以用作基于病毒相关溶酶体功能障碍的人类神经退行性变的实验模型仍不清楚。猪血凝性脑脊髓炎病毒在小鼠中表现出嗜神经性，神经细胞是其病毒进展的靶点。目前已证实PHEV感染是神经退行性疾病的危险因素。该研究结果首次证明PHEV感染可导致溶酶体疾病，并表明溶酶体功能障碍的具体机制与PGRN表达缺陷有关，并表明与PHEV感染后的人类神经退行性疾病相似的发病机制。海藻糖还可以增加颗粒蛋白前体的表达并挽救 PHEV 感染细胞中溶酶体结构的异常。总之，这些结果表明 PHEV 可能作为研究其他退行性疾病发病机制和预防的疾病模型。