Processing of the Ebola virus glycoprotein by the proprotein convertase furin

被引:389
作者
Volchkov, VE [1 ]
Feldmann, H [1 ]
Volchkova, VA [1 ]
Klenk, HD [1 ]
机构
[1] Philipps Univ Marburg, Inst Virol, D-35011 Marburg, Germany
关键词
D O I
10.1073/pnas.95.10.5762
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
in the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse-chase experiments, the mature form and two different precursors were identified. First, the endoplasmic reticulum form preGP(er), full length GP with oligomannosidic N-glycans, was detected, preGP(er) (IIO kDa) was replaced by the Golgi-specific form preGP (160 kDa), full-length GP containing mature carbohydrates, preGP was finally converted by proteolysis into mature GP(1,2), which consisted of two disulfide-linked cleavage products, the aminoterminal 140-kDa fragment GP(1), and the carboxyl-terminal 26-kDa fragment GP(2). GP(1,2) was also identified in Ebola virions. Studies employing site-directed mutagenesis revealed that GP was cleaved at a multibasic amino acid motif located at positions 497 to 501 of the ORF. Cleavage was blocked by a peptidyl chloromethylketone containing such a motif, CP is cleaved by the proprotein convertase furin. This was indicated by the observation that cleavage did not occur when GP was expressed in furin-defective LoVo cells but that it was restored in these cells by vector-expressed furin. The Reston subtype, which differs from all other Ebola viruses by its low human pathogenicity, has a reduced cleavability due to a mutation at the cleavage site. As a result of these observations, it should now be considered that proteolytic processing of GP may be an important determinant for the pathogenicity of Ebola virus.
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页码:5762 / 5767
页数:6
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