A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties

作者：Millet Jean Kaoru; Goldstein Monty E; Labitt Rachael N; Hsu Hung Lun; Daniel Susan; Whittaker Gary R^*

来源：Emerging Microbes & Infections, 2016, 5(12): e126.

DOI：10.1038/emi.2016.125

• camel
• coronavirus
• furin
• fusion activation
• MERS
• spike

Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2' fusion activation site-notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1' cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell-cell fusion and pseudotyped virus infectivity assays demonstrated that the S2' substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution.

• 出版日期2016-12-21