Kuhn Jens H, Radoshitzky Sheli R, Guth Alexander C, Warfield Kelly L, Li Wenhui, Vincent Martin J, Towner Jonathan S, Nichol Stuart T, Bavari Sina, Choe Hyeryun, Aman M Javad, Farzan Michael
Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772, USA.
J Biol Chem. 2006 Jun 9;281(23):15951-8. doi: 10.1074/jbc.M601796200. Epub 2006 Apr 4.
The GP(1,2) envelope glycoproteins (GP) of filoviruses (marburg- and ebolaviruses) mediate cell-surface attachment, membrane fusion, and entry into permissive cells. Here we show that a 151-amino acid fragment of the Lake Victoria marburgvirus GP1 subunit bound filovirus-permissive cell lines more efficiently than full-length GP1. An homologous 148-amino acid fragment of the Zaire ebolavirus GP1 subunit similarly bound the same cell lines more efficiently than a series of longer GP1 truncation variants. Neither the marburgvirus GP1 fragment nor that of ebolavirus bound a nonpermissive lymphocyte cell line. Both fragments specifically inhibited replication of infectious Zaire ebolavirus, as well as entry of retroviruses pseudotyped with either Lake Victoria marburgvirus or Zaire ebolavirus GP(1,2). These studies identify the receptor-binding domains of both viruses, indicate that these viruses utilize a common receptor, and suggest that a single small molecule or vaccine can be developed to inhibit infection of all filoviruses.
丝状病毒（马尔堡病毒和埃博拉病毒）的糖蛋白（GP）包膜糖蛋白（GP）介导细胞表面附着、膜融合以及进入易感细胞。我们在此表明，维多利亚湖马尔堡病毒GP1亚基的一个151个氨基酸的片段比全长GP1更有效地结合丝状病毒易感细胞系。扎伊尔埃博拉病毒GP1亚基的一个同源148个氨基酸的片段同样比一系列更长的GP1截短变体更有效地结合相同的细胞系。马尔堡病毒GP1片段和埃博拉病毒的片段均不结合非易感淋巴细胞系。这两个片段均特异性抑制感染性扎伊尔埃博拉病毒的复制，以及抑制用维多利亚湖马尔堡病毒或扎伊尔埃博拉病毒GP（1,2）假型化的逆转录病毒进入细胞。这些研究确定了两种病毒的受体结合结构域，表明这些病毒利用共同的受体，并提示可以开发单一小分子或疫苗来抑制所有丝状病毒的感染。
