Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor

• Published in: Nature (London) Vol. 503; no. 7477; pp. 535 - 538
• Main Authors: Ge, Xing-Yi, Li, Jia-Lu, Yang, Xing-Lou, Chmura, Aleksei A., Zhu, Guangjian, Epstein, Jonathan H., Mazet, Jonna K., Hu, Ben, Zhang, Wei, Peng, Cheng, Zhang, Yu-Ji, Luo, Chu-Ming, Tan, Bing, Wang, Ning, Zhu, Yan, Crameri, Gary, Zhang, Shu-Yi, Wang, Lin-Fa, Daszak, Peter, Shi, Zheng-Li
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.11.2013; Nature Publishing Group
• Subjects: 631/326/596/2078; Angiotensin-Converting Enzyme 2; Animals; Bats; China; Chiroptera - virology; Chlorocebus aethiops; Coronaviruses; COVID-19; Disease Reservoirs - virology; Distribution; Epidemics; Feces - virology; Fluorescent Antibody Technique; Genes; Genetic aspects; Genetic diversity; Genome, Viral - genetics; Genomes; Health aspects; Host Specificity; Humanities and Social Sciences; Humans; Identification and classification; letter; Microbiology; Molecular Sequence Data; multidisciplinary; Pandemics; Pandemics - prevention & control; Pandemics - veterinary; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Phylogenetics; Proteins; Public health; Real-Time Polymerase Chain Reaction; Receptors, Virus - genetics; Receptors, Virus - metabolism; RNA polymerase; SARS Virus - genetics; SARS Virus - isolation & purification; SARS Virus - metabolism; SARS Virus - ultrastructure; Science; Severe acute respiratory syndrome; Severe Acute Respiratory Syndrome - prevention & control; Severe Acute Respiratory Syndrome - transmission; Severe Acute Respiratory Syndrome - veterinary; Severe Acute Respiratory Syndrome - virology; Species Specificity; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - metabolism; Vero Cells; Viral genetics; Virion - isolation & purification; Virion - ultrastructure; Virus Internalization; Viverridae - metabolism; Wildlife; Zoonoses; China
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature12711

Whole-genome sequences of two novel SARS-CoV-related bat coronaviruses, in addition to a live isolate of a bat SARS-like coronavirus, are reported; the live isolate can infect human cells using ACE2, providing the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV. A SARS-like virus in bats Peter Daszak and colleagues identify two novel coronaviruses from Chinese horseshoe bats that are closely related to severe acute respiratory syndrome coronavirus (SARS-CoV), the cause of a pandemic during 2002 and 2003. They also isolate a live virus from these bats that has high sequence identity to SARS-CoV and that can infect human cells using ACE2, the same receptor that is used by SARS-CoV. The results provide the strongest evidence to date that horseshoe bats are natural reservoirs of SARS-CoV. The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history 1 . An ongoing outbreak of Middle East respiratory syndrome coronavirus 2 suggests that this group of viruses remains a key threat and that their distribution is wider than previously recognized. Although bats have been suggested to be the natural reservoirs of both viruses 3 , 4 , 5 , attempts to isolate the progenitor virus of SARS-CoV from bats have been unsuccessful. Diverse SARS-like coronaviruses (SL-CoVs) have now been reported from bats in China, Europe and Africa 5 , 6 , 7 , 8 , but none is considered a direct progenitor of SARS-CoV because of their phylogenetic disparity from this virus and the inability of their spike proteins to use the SARS-CoV cellular receptor molecule, the human angiotensin converting enzyme II (ACE2) 9 , 10 . Here we report whole-genome sequences of two novel bat coronaviruses from Chinese horseshoe bats (family: Rhinolophidae) in Yunnan, China: RsSHC014 and Rs3367. These viruses are far more closely related to SARS-CoV than any previously identified bat coronaviruses, particularly in the receptor binding domain of the spike protein. Most importantly, we report the first recorded isolation of a live SL-CoV (bat SL-CoV-WIV1) from bat faecal samples in Vero E6 cells, which has typical coronavirus morphology, 99.9% sequence identity to Rs3367 and uses ACE2 from humans, civets and Chinese horseshoe bats for cell entry. Preliminary in vitro testing indicates that WIV1 also has a broad species tropism. Our results provide the strongest evidence to date that Chinese horseshoe bats are natural reservoirs of SARS-CoV, and that intermediate hosts may not be necessary for direct human infection by some bat SL-CoVs. They also highlight the importance of pathogen-discovery programs targeting high-risk wildlife groups in emerging disease hotspots as a strategy for pandemic preparedness.