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Originally published In Press as doi:10.1074/jbc.M601796200 on April 4, 2006
J. Biol. Chem., Vol. 281, Issue 23, 15951-15958, June 9, 2006
Conserved Receptor-binding Domains of Lake Victoria Marburgvirus and Zaire Ebolavirus Bind a Common Receptor*
Jens H. Kuhn 1,
Sheli R. Radoshitzky ,
Alexander C. Guth ,
Kelly L. Warfield¶,
Wenhui Li ,
Martin J. Vincent||,
Jonathan S. Towner||,
Stuart T. Nichol||,
Sina Bavari¶,
Hyeryun Choe**,
M. Javad Aman¶, and
Michael Farzan 2
From the
Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772, the Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin, 14195 Berlin, Germany, the ¶United States Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Frederick, Maryland 21702, the ||Special Pathogens Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30222, and the **Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115
The GP1,2 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 GP1,2. 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.
Received for publication, February 24, 2006
, and in revised form, March 30, 2006.
* This work was supported in part by Grant F_X012_04_RD_B from the Defense Threat Reduction Agency. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Recipient of Career Development Fellowship Grant AI057159 from the New England Regional Center of Excellence/Biodefense and Infectious Diseases, Boston, MA.
2 To whom correspondence should be addressed: Dept. of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, 1 Pine Hill Dr., Southborough, MA 01772-9102. Tel.: 508-624-8019; Fax: 508-786-3317; E-mail: farzan{at}hms.harvard.edu.

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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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