Journal Article

A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence

Plante, Jessica A, Lanzavecchia, Antonio, Randell, Scott H, Yount, Boyd L, Shi, Zhengli-Li, Baric, Ralph S, Debbink, Kari, Menachery, Vineet D, Agnihothram, Sudhakar, Graham, Rachel L, Donaldson, Eric F, Gralinski, Lisa E, Marasco, Wayne A, Scobey, Trevor, Ge, Xing-Yi

2015

Overview

Ralph Baric, Vineet Menachery and colleagues characterize a SARS-like coronavirus circulating in Chinese horseshoe bats to determine its potential to infect primary human airway epithelial cells, cause disease in mice and respond to available therapeutics. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations 1 . Using the SARS-CoV reverse genetics system 2 , we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo . Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Publishing Group US
• Subject: 101/1 / 13/1 / 14/1 / 631/250/255/2514 / 631/326/1762 / 631/326/596/2078 / 64/60 / 692/308/575 / ACE2 / Angiotensin / Angiotensin converting enzyme / Angiotensin-converting enzyme 2 / Angiotensins / Animal experimentation / Animals / Antibodies / Antibodies, Monoclonal - immunology / Antibodies, Viral - immunology / B cells / Bats (Animals) / Biomedicine / Cancer Research / Cell Line / Chiroptera - virology / Coronavirus / Coronaviruses / COVID-19 / Disease transmission / Diseases / Enzymes / Epidemics / Epithelial cells / Epithelial Cells - pathology / Epithelial Cells - virology / Epithelium / Female / Genetics / Health aspects / Humans / Infectious Diseases / letter / Lung - virology / Metabolic Diseases / Mice, Inbred BALB C / Middle East respiratory syndrome / Molecular Medicine / Monoclonal antibodies / Neurosciences / Neutralization Tests / Novels / Pathogenesis / Peptidyl-dipeptidase A / Phylogeny / Replication / Respiratory diseases / Respiratory tract / Respiratory tract diseases / SARS coronavirus / SARS Virus - immunology / SARS Virus - pathogenicity / SARS Virus - physiology / Severe acute respiratory syndrome / Severe Acute Respiratory Syndrome - virology / Spike protein / Therapeutics / Viral diseases / Virulence / Virus Replication / Viruses