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Journal of Virology, March 2004, p. 2943-2947, Vol. 78, No. 6
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.6.2943-2947.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Human Macrophage C-Type Lectin Specific for Galactose and N-Acetylgalactosamine Promotes Filovirus Entry
Ayato Takada,1,2 Kouki Fujioka,3 Makoto Tsuiji,3 Akiko Morikawa,3 Nobuaki Higashi,3 Hideki Ebihara,4 Darwyn Kobasa,4 Heinz Feldmann,5 Tatsuro Irimura,3 and Yoshihiro Kawaoka1,2,4*
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639,1
CREST, Japan Science and Technology Corporation, Saitama 332-0012,2
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan,3
Department of Pathobiological Sciences, University of Wisconsin, Madison, Wisconsin 53706,4
Special Pathogens Program, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Winnipeg, Manitoba R3E 3R2, Canada5
Received 10 July 2003/
Accepted 24 November 2003
Filoviruses cause lethal hemorrhagic disease in humans and nonhuman primates. An initial target of filovirus infection is the mononuclear phagocytic cell. Calcium-dependent (C-type) lectins such as dendritic cell- or liver/lymph node-specific ICAM-3 grabbing nonintegrin (DC-SIGN or L-SIGN, respectively), as well as the hepatic asialoglycoprotein receptor, bind to Ebola or Marburg virus glycoprotein (GP) and enhance the infectivity of these viruses in vitro. Here, we demonstrate that a recently identified human macrophage galactose- and N-acetylgalactosamine-specific C-type lectin (hMGL), whose ligand specificity differs from DC-SIGN and L-SIGN, also enhances the infectivity of filoviruses. This enhancement was substantially weaker for the Reston and Marburg viruses than for the highly pathogenic Zaire virus. We also show that the heavily glycosylated, mucin-like domain on the filovirus GP is required for efficient interaction with this lectin. Furthermore, hMGL, like DC-SIGN and L-SIGN, is present on cells known to be major targets of filoviruses (i.e., macrophages and dendritic cells), suggesting a role for these C-type lectins in viral replication in vivo. We propose that filoviruses use different C-type lectins to gain cellular entry, depending on the cell type, and promote efficient viral replication.
* Corresponding author. Mailing address: Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 608-265-4925. Fax: 608-265-5622. E-mail:
kawaoka{at}ims.u-tokyo.ac.jp.
Journal of Virology, March 2004, p. 2943-2947, Vol. 78, No. 6
0022-538X/04/$08.00+0 DOI: 10.1128/JVI.78.6.2943-2947.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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