Emergence of an ancient and pathogenic mammarenavirus

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 IFN alpha beta R-/- 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).

Automated summary

Emerging zoonoses of wildlife origin pose a significant threat to human health, and the Qinghai-Tibet Plateau is an important hotspot for such diseases. In this study, a novel arenavirus named plateau pika virus (PPV) was identified and characterized from plateau pikas. PPV strains could replicate in mammalian cells and led to tremors, sudden death, and inflammatory brain lesions in IFN alpha beta R-/- mice. Serological surveys also found PPV-specific IgG antibodies in a small percentage of outpatients in the region where PPV was isolated. Phylogenetic analysis revealed that PPV is distinct from known mammarenaviruses and originated millions of years ago.