Department of Genetics, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
Department of Genetics, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
Cell Rep. 2019 Apr 30;27(5):1387-1396.e5. doi: 10.1016/j.celrep.2019.04.004.
Arenaviruses can cause severe hemorrhagic disease in humans, which can progress to organ failure and death. The underlying mechanisms causing lethality and person-to-person variation in outcome remain incompletely explained. Herein, we characterize a mouse model that recapitulates many features of pathogenesis observed in humans with arenavirus-induced hemorrhagic disease, including thrombocytopenia, severe vascular leakage, lung edema, and lethality. The susceptibility of congenic B6.PL mice to lymphocytic choriomeningitis virus (LCMV) infection is associated with increased antiviral T cell responses in B6.PL mice compared with C57BL/6 mice and is T cell dependent. Pathogenesis imparted by the causative locus is inherited in a semi-dominant manner in F1 crosses. The locus includes PL-derived sequence variants in both poorly annotated genes and genes known to contribute to immune responses. This model can be used to further interrogate how limited genetic differences in the host can remarkably alter the disease course of viral infection.
沙粒病毒可引起人类严重出血性疾病，进而导致器官衰竭和死亡。导致致死率和个体间结局差异的潜在机制仍不完全清楚。在此，我们描述了一种小鼠模型，该模型再现了人类沙粒病毒引起的出血性疾病中观察到的许多发病特征，包括血小板减少、严重的血管渗漏、肺水肿和致死率。与 C57BL/6 小鼠相比，同源 B6.PL 小鼠对淋巴细胞性脉络丛脑膜炎病毒 (LCMV) 感染的易感性与 B6.PL 小鼠中抗病毒 T 细胞反应增加有关，并且依赖于 T 细胞。在 F1 杂交中，由致病基因座赋予的发病机制以半显性方式遗传。该基因座包含在注释不完善的基因和已知对免疫反应有贡献的基因中都存在 PL 衍生的序列变异。该模型可用于进一步研究宿主中有限的遗传差异如何显著改变病毒感染的疾病进程。
