Abstract

Viruses mutate and form quasispecies within the host, from which the next generation is selected. Studying the selected mutations of an animal virus across different host species can aid in predicting how the virus might evolve to manage future potential pandemics in humans. In this study, both high-passaged (p44) and low-passaged (p4) Shaan viruses of bat origin in MARC-145 cell lines, derived from African green monkey kidney, were passaged once into human A549, HEK-293, and HRT-18 cell lines as different host species models. High-throughput sequencing data showed that there were distinct selected mutations and single nucleotide variants (SNVs) between the low- and high-passaged Shaan viruses in MARC-145 cells. After host switching, these mutation patterns were consistently observed among the same host cells in triplicate experiments, suggesting a host cell-specific selection pattern for the progeny of Shaan viruses. Notably, HRT-18 cells of colorectal adenocarcinoma origin produced more unique selected mutations and unique SNVs. While Shaan virus-specific transcripts associated with the N gene were most abundant in MARC-145, A549, and HEK-293 cells, those associated with the M gene were most abundant in HRT-18 cells. After host switching, the relative viral RNA levels in the HRT-18 cells were significantly higher than in A549 and HEK-293 cells. Thus, this study provides evidence of host-specific mutation patterns by cell type and host cells in the evolution of Shaan virus.