Emergence of an ancient and pathogenic mammarenavirus

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).

The ever-expanding diversity and complexity of the Arenaviridae family

“…TCRV) have also been found in Artibeus neotropical leaf-nosed, fruit-eating bats of the Phyllostomidae family [ 10 ]. The plateau pika viruses (PPVs) were found in small, mountain-dwelling mammals called pikas in Asia and Southeast Asia [ 11 , 12 ]. Other mammals, such as the Northern white-breasted hedgehogs in Hungary (Europe), serve as natural hosts for the Mecsek Mountains virus MEMV [ 13 ].…”

CD71: Role in permafrost immunity

“…Case in point, a novel arenavirus, named the Plateau Pika virus (PPV), which is capable of infecting mammalian cells, was recently obtained from the plateau pikas (Ochotona curzoniae) on the Qinghai-Tibet Plateau. Phylogenetic analyses revealed that PPV is a very ancient mammarenavirus that diverged from today's lines of New and Old World mammarenaviruses about 77-88 million years ago [ 36 ].…”

Recent Discoveries of Novel Mammarenaviruses Infecting Humans and Other Mammals in Asia and Southeast Asia

“…They are most commonly transmitted by unintentional human contacts with infected virus-ladened rodent urine, droppings, or nesting materials [ 1 ]. Mammarenaviruses are generally divided into two groups, New World and Old World, based on their phylogenetic, serological, and geographical differences [ 4 ]. New World (NW) mammarenaviruses, including several known human pathogens, such as Junin, Machupo, Sabia, Chapare, and Guanarito viruses, are found in North and South America in rodent subfamilies Sigmodontiae and Muridae .…”

“…More recently, another novel mammarenavirus, called Plateau Pika Virus (PPV), has been isolated from plateau pikas, which are small mammals of the Lagomorpha family, in the Qinghai Tibet Plateau region [ 3 ]. Based on phylogenetic analyses of the genetic sequences of the viral matrix Z protein, the RNA-dependent RNA polymerase (RdRp) L protein, glycoprotein (GP), and nucleoprotein (NP), it is likely that PPV diverged between 77 and 88 million years ago, which would place this newly identified mammarenavirus in a separate lineage that appeared long before the divergence of OW and NW mammarenaviruses ( Figure 1 ) [ 4 ]. RNA sequencing of plateau pika intestinal contents revealed PPV RNA in 34 of 541 (6.3%) of the samples analysed.…”

“…RNA sequencing of plateau pika intestinal contents revealed PPV RNA in 34 of 541 (6.3%) of the samples analysed. Serological screening of human sera detected antibodies in 8 of 335 (2.4%) samples [ 4 ]. PPV was shown to infect and replicate in multiple mammalian cell lines, including human, primate, and rodent cells, suggesting that the host range of PPV could spread beyond rodents and small mammals if exposed to new hosts.…”