SARS-like WIV1-CoV poised for human emergence

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 11; pp. 3048 - 3053
• Main Authors: Menachery, Vineet D., Yount, Boyd L., Sims, Amy C., Debbink, Kari, Agnihothram, Sudhakar S., Gralinski, Lisa E., Graham, Rachel L., Scobey, Trevor, Plante, Jessica A., Royal, Scott R., Swanstrom, Jesica, Sheahan, Timothy P., Pickles, Raymond J., Corti, Davide, Randell, Scott H., Lanzavecchia, Antonio, Marasco, Wayne A., Baric, Ralph S.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15.03.2016; National Acad Sciences
• Series: From the Cover
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Biological Sciences; Cells, Cultured; Cercopithecus aethiops; Chiroptera - virology; Communicable Diseases, Emerging - virology; Coronaviridae - genetics; Coronaviridae - immunology; Coronaviridae - isolation & purification; Coronaviridae - pathogenicity; Coronaviridae - physiology; Coronaviridae Infections - prevention & control; Coronaviridae Infections - transmission; Coronaviridae Infections - veterinary; Coronaviridae Infections - virology; Cross Reactions; Encephalitis, Viral - virology; Epithelial Cells - virology; Genetics; Genomics; Global economy; Host Specificity; Human populations; Humans; Lung - cytology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Models, Molecular; Monoclonal antibodies; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - physiology; Point Mutation; Protein Conformation; Reagents; Receptors, Virus - genetics; Receptors, Virus - physiology; Recombinant Fusion Proteins - metabolism; SARS coronavirus; SARS Virus - immunology; Severe acute respiratory syndrome; Species Specificity; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - physiology; Vero Cells; Virus Replication; Viruses; Zoonoses; Spike; SARS; CoV; WIV1; emergence
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1517719113

Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies,methods to leverage these datasets to identify future threats are underdeveloped. In this study, we describe an approach that combines existing metagenomics data with reverse genetics to engineer reagents to evaluate emergence and pathogenic potential of circulating zoonotic viruses. Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations. However, in vivo attenuation suggests additional adaptation is required for epidemic disease. Importantly, available SARS monoclonal antibodies offered success in limiting viral infection absent from available vaccine approaches. Together, the data highlight the utility of a platform to identify and prioritize prepandemic strains harbored in animal reservoirs and document the threat posed by WIV1-CoV for emergence in human populations.