ABSTRACT

Emerging zoonoses of wildlife origin caused by previously unknown agents are one of the most important challenges for human health. The Qinghai-Tibet Plateau represents a unique ecological niche with diverse wildlife that harbours several human pathogens and numerous previously uncharacterized pathogens. In this study, we identified and characterized a novel arenavirus (namely, plateau pika virus, PPV) from plateau pikas (Ochotona curzoniae) on the Qinghai-Tibet Plateau by virome analysis. Isolated PPV strains could replicate in several mammalian cells. We further investigated PPV pathogenesis using animal models. PPV administered via an intraventricular route caused trembling and sudden death in IFNαβR^-/- mice, and pathological inflammatory lesions in brain tissue were observed. According to a retrospective serological survey in the geographical region where PPV was isolated, PPV-specific IgG antibodies were detected in 8 (2.4%) of 335 outpatients with available sera. Phylogenetic analyses revealed that this virus was clearly separated from previously reported New and Old World mammarenaviruses. Under the co-speciation framework, the estimated divergence time of PPV was 77–88 million years ago (MYA), earlier than that of OW and NW mammarenaviruses (26-34 MYA).

摘要

由以前未知的病原体引起的野生动物源性人畜共患病是人类健康面临的最重要挑战之一。青藏高原代表着独特的生态位，拥有多种野生动物，其中蕴藏着多种人类病原体和许多以前未知的病原体。在本研究中，我们通过病毒组分析从青藏高原鼠兔（ Ochotona curzoniae）中鉴定并鉴定了一种新型沙粒病毒（即高原鼠兔病毒，PPV） 。分离的 PPV 菌株可以在多种哺乳动物细胞中复制。我们使用动物模型进一步研究了 PPV 发病机制。通过心室内途径施用 PPV 导致 IFNαβR 颤抖和猝死^-/-小鼠，观察脑组织病理性炎症病变。根据对PPV分离地区的回顾性血清学调查，在335名门诊患者的可用血清中，有8名（2.4%）检测到PPV特异性IgG抗体。系统发育分析表明，该病毒与之前报道的新世界和旧世界乳房病毒明显分开。在共物种框架下，PPV的估计分化时间为77-8800万年前（MYA），早于OW和NW哺乳动物病毒（26-34 MYA）。