The 2002–3 pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV) was one of the most significant public health events in recent history1. An ongoing outbreak of Middle East respiratory syndrome coronavirus2 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 viruses3,4,5, 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 Africa5,6,7,8, 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.
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Sequences of three bat SL-CoV genomes, bat SL-CoV RBD and R. sinicus ACE2 genes have been deposited in GenBank under accession numbers KC881005–KC881007 (genomes from SL-CoV RsSHC014, Rs3367 and W1V1, respectively), KC880984–KC881003 (bat SL-CoV RBD genes) and KC881004 (R. sinicus ACE2), respectively.
We acknowledge financial support from the State Key Program for Basic Research (2011CB504701 and 2010CB530100), National Natural Science Foundation of China (81290341 and 31321001), Scientific and technological basis special project (2013FY113500), CSIRO OCE Science Leaders Award, National Institute of Allergy and Infectious Diseases (NIAID) award number R01AI079231, a National Institutes of Health (NIH)/National Science Foundation (NSF) ‘Ecology and Evolution of Infectious Diseases’ award from the NIH Fogarty International Center (R01TW005869), an award from the NIH Fogarty International Center supported by International Influenza Funds from the Office of the Secretary of the Department of Health and Human Services (R56TW009502), and United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT. The contents are the responsibility of the authors and do not necessarily reflect the views of NIAID, NIH, NSF, USAID or the United States Government. We thank X. Che from Zhujiang Hospital, Southern Medical University, for providing human SARS patient sera.
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