The genomic characteristics and pathogenicity of a mammalian orthoreovirus within a new lineage from wild pika in plateau

Emerging and re-emerging viruses from wild animals have seriously threatened the health of humans and domesticated animals in recent years. Herein, we isolated a new mammalian orthoreovirus (MRV), Pika/MRV/ GCCDC7/2019 (PMRV-GCCDC7), in the Qinghai-Tibet Plateau wild pika (Ochotona curzoniae). Though the PMRVGCCDC7 shows features of a typical reovirus with ten gene segments arranged in 3:3:4 in length, the virus belongs to an independent evolutionary branch compared to other MRVs based on phylogenetic tree analysis. The results of cellular susceptibility, species tropism, and replication kinetics of PMRV-GCCDC7 indicated the virus could infect four human cell lines (A549, Huh7, HCT, and LoVo) and six non-human cell lines, including Vero-E6, LLCMK2, BHK-21, N2a, MDCK, and RfKT cell, derived from diverse mammals, i.e. monkey, mice, canine and bat, which revealed the potential of PMRV-GCCDC7 to infect a variety of hosts. Infection of BALB/c mice with PMRVGCCDC7 via intranasal inoculation led to relative weight loss, lung tissue damage and inflammation with the increase of virus titer, but no serious respiratory symptoms and death occurred. The characterization of the new reovirus from a plateau-based wild animal has expanded our knowledge of the host range of MRV and provided insight into its risk of trans-species transmission and zoonotic diseases.