middle east respiratory syndrome coronavirus nonstructural protein 16 is necessary for interferon resistance and viral pathogenesis

• DOI: 10.17615/spqv-hy42
• Publication Date: 2017-12-27
• Authors: Boyd Yount; Sarah R. Leist; Lisa E. Gralinski; Kenneth H. Dinnon; Adam S. Cockrell; Hugh D. Mitchell; Ralph S. Baric; Amy C. Sims; Rachel L. Graham; Eileen T. McAnarney; Eileen T. McAnarney; Vineet D. Menachery; Vineet D. Menachery; Katrina M. Waters; Kelly G. Stratton; Kari Debbink
• Keywords: emerging virus; 0301 basic medicine; MERS-CoV; 03 medical and health sciences; IFIT; coronavirus; SARS-CoV; live attenuated; Microbiology; QR1-502; Research Article; 3. Good health

Coronavirus (CoV) emergence in both humans and livestock represents a significant threat to global public health, as evidenced by the sudden emergence of severe acute respiratory syndrome CoV (SARS-CoV), MERS-CoV, porcine epidemic diarrhea virus, and swine delta CoV in the 21st century. These studies describe an approach that effectively targets the highly conserved 2′ O -MTase activity of CoVs for attenuation. With clear understanding of the IFN/IFIT (IFN-induced proteins with tetratricopeptide repeats)-based mechanism, NSP16 mutants provide a suitable target for a live attenuated vaccine platform, as well as therapeutic development for both current and future emergent CoV strains. Importantly, other approaches targeting other conserved pan-CoV functions have not yet proven effective against MERS-CoV, illustrating the broad applicability of targeting viral 2′ O -MTase function across CoVs.