A型塞内卡病毒C57BL/6JIFNR-/-小鼠感染模型建立及感染特性评价

Establishment of a Senecavirus A infection model in C57BL/6JIFNAR-/- mice and evaluation of its infection characteristics

摘要:

目的 构建能有效模拟猪A型塞内卡病毒(Senecavirus A, SVA)关键临床特征的小鼠模型，为阐明其致病机制及开展防控产品评价提供关键实验工具。方法 通过腹腔、皮下、肌内注射3种途径分别接种5周龄SPF级C57BL/6J野生型(WT)小鼠和I型干扰素受体缺失(C57BL/6J^IFNR-/-)小鼠，于感染后第1、3、5天采集血液及组织样本，进行宏观病理、组织病理、病毒载量及炎性因子mRNA动态检测。结果 与未接毒对照组相比，2种小鼠均出现腹股沟淋巴结肿大、肝脏土黄色变及脾肿大等宏观病变和显微病变(淋巴结皮质崩解、肝细胞坏死、脾白髓萎缩、肾小管坏死)，但C57BL/6J^IFNR-/-小鼠病变更为严重；病毒RNA在2种小鼠组织中广泛分布，但C57BL/6J^IFNR-/-组显著高于WT组。此外，WT小鼠未出现病毒血症，C57BL/6J^IFNR-/-小鼠在感染后1 dpi全血中即可检出病毒，3 dpi达到峰值后快速下降。炎症因子检测显示，C57BL/6J^IFNR-/-小鼠IL-1β和IL-6炎性因子mRNA水平和蛋白水平均显著高于WT小鼠。结论 C57BL/6J^IFNR-/-小鼠首次模拟了猪SVA短暂病毒血症特征，可全面复现病毒多器官分布、高病毒载量及自限性恢复等特征，为深入研究其致病机制及评价疫苗与抗病毒药物提供了更为有效的动物模型。

Abstract:

Objective To establish a mouse model that effectively simulates the key clinical features of porcine Senecavirus A (SVA) infection, providing a crucial experimental tool for elucidating its pathogenesis and evaluating prevention and control products.Methods Five-week-old SPF C57BL/6J wild-type (WT) mice and type I interferon receptor-deficient (C57BL/6J^IFNR-/-) mice were inoculated via intraperitoneal, subcutaneous, and intramuscular routes. Blood and tissue samples were collected on days 1, 3, and 5 post-infection (dpi) for analysis of gross pathology, histopathology, viral load, and dynamic determination of inflammatory cytokines at the mRNA level.Results Compared with the mock-infected control group, both mouse strains developed gross lesions (e.g., swollen inguinal lymph nodes, yellowish livers, splenomegaly) and histopathological lesions (e.g., cortical disintegration of lymph nodes, hepatocellular necrosis, atrophy of splenic white pulp, and renal tubular necrosis). However, these lesions were more severe in C57BL/6J^IFNR-/- mice. Viral RNA was widely distributed in tissues of both groups but was significantly higher in the C57BL/6J^IFNR-/- group. Notably, viremia was undetectable in WT mice, whereas in C57BL/6J^IFNR-/- mice, the virus was detected in whole blood as early as 1 dpi, peaked at 3 dpi, and then declined rapidly. Inflammatory cytokine analysis revealed significantly higher mRNA levels and protein levels of IL-1β and IL-6 in C57BL/6J^IFNR-/- mice than in WT mice.Conclusion The C57BL/6J^IFNR-/- mouse model successfully simulates, for the first time, the transient viremia characteristic of porcine SVA infection. It comprehensively replicates key features, including the multi-organ viral distribution, high viral load, and self-limiting recovery, providing a more effective animal model for delving into the pathogenic mechanism of SVA and evaluating vaccines and antiviral drugs.