Middle East respiratory syndrome coronavirus (MERS-CoV) has represented a human health threat since 2012. Although several MERS-related CoVs that belong to the same species as MERS-CoV have been identified from bats, they do not use the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4). Here, we screened 1,059 bat samples from at least 30 bat species collected in different regions in south China and identified 89 strains of lineage C betacoronaviruses, including Tylonycteris pachypus coronavirus HKU4, Pipistrellus pipistrellus coronavirus HKU5, and MERSrelated CoVs. We sequenced the full-length genomes of two positive samples collected from the great evening bat, Ia io, from Guangdong Province. The two genomes were highly similar and exhibited genomic structures identical to those of other lineage C betacoronaviruses. While they exhibited genome-wide nucleotide identities of only 75.3 to 81.2% with other MERS-related CoVs, their gene-coding regions were highly similar to their counterparts, except in the case of the spike proteins. Further protein-protein interaction assays demonstrated that the spike proteins of these MERS-related CoVs bind to the receptor DPP4. Recombination analysis suggested that the newly discovered MERS-related CoVs have acquired their spike genes from a DPP4-recognizing bat coronavirus HKU4. Our study provides further evidence that bats represent the evolutionary origins of MERS-CoV.
Bibliographical noteFunding Information:
We thank Lanying Du for the mouse antiserum and monoclonal antibody against MERS-CoV-spike. This study was jointly funded by the Scientific and Technological Basis Special Project (2013FY113500) from the Ministry of Science and Technology of the People’s Republic of China to Z.-L.S., a USAID Emerging Pandemic Threats PREDICT project grant (Cooperative Agreement no. AID-OAA-A-14-00102), NIH grants (R01AI110964 to Z.-L.S.; R01AI089728 and R01AI110700 to F.L.), and the National Natural Science Foundation of China (31727901) to Z.-L.S.
- Dipeptidyl peptidase 4
- MERS-related coronavirus
- Virus discovery