Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus

• Published in: PLoS pathogens Vol. 13; no. 11; p. e1006698
• Main Authors: Hu, Ben, Zeng, Lei-Ping, Yang, Xing-Lou, Ge, Xing-Yi, Zhang, Wei, Li, Bei, Xie, Jia-Zheng, Shen, Xu-Rui, Zhang, Yun-Zhi, Wang, Ning, Luo, Dong-Sheng, Zheng, Xiao-Shuang, Wang, Mei-Niang, Daszak, Peter, Wang, Lin-Fa, Cui, Jie, Shi, Zheng-Li
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.11.2017; Public Library of Science (PLoS)
• Subjects: Amino Acid Sequence - genetics; Animals; Bats; Biology and life sciences; Chiroptera; Chiroptera - virology; Coronaviridae; Coronavirus Infections - virology; Coronaviruses; COVID-19; Evolution, Molecular; Five year plans; Funding; Gene Pool; Genes; Genome, Viral - genetics; Genomes; Humans; Infectious diseases; Laboratories; Medicine and health sciences; Proteins; Recombination; Recombination, Genetic - genetics; Research and Analysis Methods; S gene; S1 gene; SARS Virus - genetics; Severe acute respiratory syndrome; Severe Acute Respiratory Syndrome - virology; Surveillance; Virology; China
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006698

A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.