期刊
NATURE MEDICINE
卷 21, 期 12, 页码 1508-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3985
关键词
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资金
- National Institute of Allergy & Infectious Disease
- National Institute of Aging of the US National Institutes of Health (NIH) [U19AI109761, U19AI107810, AI085524, F32AI102561, K99AG049092]
- National Natural Science Foundation of China [81290341, 31470260]
- USAID-EPT-PREDICT from EcoHealth Alliance
- National Institute of Diabetes and Digestive and Kidney Disease of the NIH [NIH DK065988]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI109761, U19AI107810, T32AI007528, R01AI085524, F32AI102561] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK065988] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [K99AG049092] Funding Source: NIH RePORTER
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.
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