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
- ‡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
- 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.
Abstract
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.
Footnotes
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↵3 The abbreviations used are: GP, glycoprotein; CoV, coronavirus; FITC, fluorescein isothiocyanate; GFP, green fluorescent protein; HIV-1, human immunodeficiency virus, type 1; MARV-Ang, Lake Victoria marburgvirus strain Angola; MARV-Mus, Lake Victoria marburgvirus strain Musoke; MLV, Moloney murine leukemia virus; PBS, phosphate-buffered saline; RBD, receptor-binding domain; SARS, severe acute respiratory syndrome; VSV, vesicular stomatitis Indiana virus; ZEBOV-May, Zaire ebolavirus strain Mayinga; ORF, open reading frame.
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↵* 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.
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↵1 Recipient of Career Development Fellowship Grant AI057159 from the New England Regional Center of Excellence/Biodefense and Infectious Diseases, Boston, MA.
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- Received February 24, 2006.
- Revision received March 30, 2006.
- The American Society for Biochemistry and Molecular Biology, Inc.
