PLoS Pathog12(2):e1005455 2016/02/22

Nelson Bay orthoreoviruses (NBVs) are members of the fusogenic orthoreoviruses that have various host species, including reptiles, birds, and mammals. Recently, several NBV strains have been isolated from patients with acute respiratory tract infections. Isolation of these pathogenic reoviruses raises concerns about the potential emerging infections of bat-borne orthoreoviruses in humans. To date, no strategy has been developed to rescue infectious viruses from cloned cDNA for any member of the fusogenic orthoreoviruses. In this study, we developed a plasmid-based reverse genetics system for a pathogenic NBV strain. We used this system to generate viruses incapable of expressing the cell attachment protein σC. Our studies using σC-deficient viruses suggest that NBVs may engage multiple independent viral ligands and cellular receptors for efficient cell attachment and viral pathogenesis, thus providing new insight into the biology of orthoreoviruses. The reverse genetics approach described in this study can be exploited for fusogenic orthoreovirus biology and used to develop vaccines, diagnostics, and therapeutics.