A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties
作者： Jean Kaoru Millet , Monty E Goldstein , Rachael N Labitt , Hung-Lun Hsu , Susan Daniel
DOI: 10.1038/EMI.2016.125
关键词: Molecular biology 、 Protease 、 Coronavirus 、 Viral entry 、 Furin 、 Tissue tropism 、 Biology 、 Virology 、 Cleavage (embryo) 、 Virus 、 Middle East respiratory syndrome coronavirus
摘要: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, the origin evolution of virus remain unclear. Here we characterize spike protein a camel-derived MERS-CoV (NRCE-HKU205) identified 2013, early MERS outbreak. NRCE-HKU205 has variant cleavage motif with regard S2' fusion activation site-notably, novel substitution isoleucine for otherwise invariant serine at critical P1' site position. The substitutions resulted loss furin-mediated cleavage, as shown by fluorogenic peptide western blot assays. Cell-cell pseudotyped infectivity assays demonstrated that decreased spike-mediated viral entry. However, cathepsin trypsin-like protease were retained, albeit much reduced efficiency compared prototypical EMC/2012 human strain. We show more limited properties possibly resulting restricted tropism may represent an intermediate complex pattern ecology evolution.
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sci-hub.se 参考文章(27)
Beth N. Licitra, Donald W. Lee, Gary R. Whittaker, Kelly L. Sams, Feline coronaviruses associated with feline infectious peritonitis have modifications to spike protein activation sites at two discrete positions arXiv: Genomics. ,(2014)
Neil D Rawlings, Alan J Barrett, Robert Finn, None, Twenty years of the MEROPS database of proteolytic enzymes, their substrates and inhibitors Nucleic Acids Research. ,vol. 44, pp. 343- 350 ,(2016) , 10.1093/NAR/GKV1118
Christine Burkard, Monique H. Verheije, Oliver Wicht, Sander I. van Kasteren, Frank J. van Kuppeveld, Bart L. Haagmans, Lucas Pelkmans, Peter J. M. Rottier, Berend Jan Bosch, Cornelis A. M. de Haan, Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner PLoS Pathogens. ,vol. 10, pp. e1004502- ,(2014) , 10.1371/JOURNAL.PPAT.1004502
S. Belouzard, V. C. Chu, G. R. Whittaker, Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 106, pp. 5871- 5876 ,(2009) , 10.1073/PNAS.0809524106
Kazuya Shirato, Miyuki Kawase, Shutoku Matsuyama, Middle East Respiratory Syndrome Coronavirus Infection Mediated by the Transmembrane Serine Protease TMPRSS2 Journal of Virology. ,vol. 87, pp. 12552- 12561 ,(2013) , 10.1128/JVI.01890-13
Maged G. Hemida, Daniel K.W. Chu, Leo L.M. Poon, Ranawaka A.P.M. Perera, Mohammad A. Alhammadi, Hoi-yee Ng, Lewis Y. Siu, Yi Guan, Abdelmohsen Alnaeem, Malik Peiris, MERS Coronavirus in Dromedary Camel Herd, Saudi Arabia Emerging Infectious Diseases. ,vol. 20, pp. 1231- 1234 ,(2014) , 10.3201/EID2007.140571
V. M. Corman, N. L. Ithete, L. R. Richards, M. C. Schoeman, W. Preiser, C. Drosten, J. F. Drexler, Rooting the phylogenetic tree of Middle East respiratory syndrome coronavirus by characterization of a conspecific virus from an African bat Journal of Virology. ,vol. 88, pp. 11297- 11303 ,(2014) , 10.1128/JVI.01498-14
Peter Duckert, Søren Brunak, Nikolaj Blom, Prediction of proprotein convertase cleavage sites Protein Engineering Design & Selection. ,vol. 17, pp. 107- 112 ,(2004) , 10.1093/PROTEIN/GZH013
Sun Tian, Wang Huajun, Jianhua Wu, Computational prediction of furin cleavage sites by a hybrid method and understanding mechanism underlying diseases Scientific Reports. ,vol. 2, pp. 261- 261 ,(2012) , 10.1038/SREP00261
Beth N. Licitra, Jean K. Millet, Andrew D. Regan, Brian S. Hamilton, Vera D. Rinaldi, Gerald E. Duhamel, Gary R. Whittaker, Mutation in spike protein cleavage site and pathogenesis of feline coronavirus. Emerging Infectious Diseases. ,vol. 19, pp. 1066- 1073 ,(2013) , 10.3201/EID1907.121094