Hayato Harima, Tokyo University of Agriculture and Technology

Hayato Harima1, Michihito Sasaki2,3, Takeshi Kobayashi4, Hirofumi Sawa2,3 1.Faculty of Agriculture, Tokyo University of Agriculture and Technology 2.International Institute for Zoonosis Control, Hokkaido University 3.Institute for Vaccine Research and Development, Hokkaido University 4.Research Institute for Microbial Diseases, Osaka University

Pathogenesis and Immunity

Pteropine orthoreovirus (PRV) is an emerging bat-borne zoonotic virus that causes severe respiratory illness in humans in Southeast Asia. We reported that PRV Nachunsulwe-57 strain (N57) isolated from a fruit bat in Zambia was less pathogenic in mice than PRV Miyazaki-Bali/2007 strain (MB) isolated from a patient in Asia. The aim of the present study was to identify viral factors that define the difference in pathogenicity between these PRV strains. Ten monoreassortant PRVs were synthesized by reverse genetics and intranasally inoculated into BALB/c mice. Compared to wild-type MB inoculation group, MB-based monoreassortants bearing the L1, S1, or S2 segments of N57 attenuated in mice, and decreased viral loads and cytokine gene expression in the lungs. This result indicates that λC and σA encoded in the L1 and S2 segments, respectively, are involved in the PRV virulence as novel factors. To identify σA residues responsible for the pathogenicity, MB-based recombinants in which the σA gene mutations were introduced into different amino acid sequences between these strains were compared for their pathogenicity in mice. The S46N, S49Y, and T54A mutations in σA increased the survival rate of the mice and decreased the viral loads and cytokine gene expression in the lungs. Taken together, our findings provide novel insights into the pathogenesis of PRV infection, and further studies are required to elucidate the molecular mechanisms that regulate by the identified virulence factors.