Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry.
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.
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Ayato
A
Takada
Kouki
K
Fujioka
Makoto
M
Tsuiji
Akiko
A
Morikawa
Nobuaki
N
Higashi
Hideki
H
Ebihara
Darwyn
D
Kobasa
Heinz
H
Feldmann
Tatsuro
T
Irimura
Yoshihiro
Y
Kawaoka
D000116:Acetylgalactosamine / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D016563:Filoviridae / Q000472:pathogenicity*; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D014709:Vero Cells
D037181:Lectins, C-Type; D000116:Acetylgalactosamine; D005690:Galactose