Tupaia orthoreovirus: The first successful isolation of a novel Mammalian orthoreovirus from treeshrews in Malaysia

Treeshrews, which share a closer common ancestor with primates and flying lemurs than with rodents, have been proposed as a better animal model for biomedical research compared to traditional rodent models. Zoonotic viruses like Mammalian orthoreovirus (MRV) pose potential public health risks, but their prevalence and characteristics in treeshrews remain underexplored. This study reports the first isolation of a novel MRV from common treeshrews (Tupaia glis) in Malaysia and investigates its biological properties. Faecal and urine samples from common treeshrews were collected and processed through centrifugation and sterile filtration. The processed samples were inoculated into mammalian cell cultures for virus isolation using a novel virus isolation protocol. The isolated virus was sequenced and analysed phylogenetically. A novel MRV, designated MRV1UNM, was isolated and identified as MRV serotype 3 (MRV3) with a unique genomic profile. Syncytial formation was observed in Vero cells during early passages only. MRV1UNM infected a broad spectrum of cell lines, including some cancer cells, causing cell lysis within days without establishing persistent infections. Moreover, increased caspase 3/7 activity was also observed in the infected A549 cells. These findings provide evidence of the oncolytic potential of MRV1UNM. In conclusion, this study reports the first isolation of MRV from Malaysian treeshrews, highlighting their role as potential reservoirs for zoonotic viruses. The promising potential of MRV1UNM as a candidate for oncolytic virotherapy warrants further investigation into its therapeutic applications.