SARS like WIV1 CoV poised for human emergence
Significance The emergence of severe acute respiratory syndrome coronavirus (SARS CoV) and Middle East respiratory syndrome (MERS) CoV highlights the continued risk of cross species transmission leading to epidemic disease. This manuscript describes efforts to extend surveillance beyond sequence analysis, constructing chimeric and full length zoonotic coronaviruses to evaluate emergence potential. Focusing on SARS like virus sequences isolated from Chinese horseshoe bats, the results indicate a significant threat posed by WIV1 CoV. Both full length and chimeric WIV1 CoV readily replicated efficiently in human airway cultures and in vivo, suggesting capability of direct transmission to humans. In addition, while monoclonal antibody treatments prove effective, the SARS based vaccine approach failed to confer protection. Together, the study indicates an ongoing threat posed by WIV1 related viruses and the need for continued study and surveillance. 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.
Proceedings of the National Academy of Sciences