Identification and characterization of carbohydrate molecules in mammalian cells recognized by dengue virus type 2.
The interaction between cell surface receptors and the envelope glycoprotein (EGP) on the viral membrane surface is the initial step of Dengue virus infection. To understand the host range, tissue tropism, and virulence of this pathogen, it is critical to elucidate the molecular mechanisms of the interaction of EGP with receptor molecules. Here, using a TLC/virus-binding assay, we isolated and characterized a carbohydrate molecule on mammalian cell surfaces that is recognized by dengue virus type 2 (DEN2). Structural determination by immunochemical methods showed that the carbohydrate structure of the purified glycosphingolipid was neolactotetraosylceramide (nLc4Cer). This glycosphingolipid was expressed on the cell surface of susceptible cells, such as human erythroleukemia K562 and baby hamster kidney BHK-21. All serotypes of DEN viruses, DEN1 to DEN4, reacted with nLc4Cer, and the non-reducing terminal disaccharide residue Galbeta1-4GlcNAcbeta1- was found to be a critical determinant for the binding of DEN2. Chemically synthesized derivatives carrying multiple carbohydrate residues of nLc4, but not nLc4 oligosaccharide, inhibited DEN2 infection of BHK-21 cells. These findings strongly suggested that multivalent nLc4 oligosaccharide could act as a competitive inhibitor against the binding of DEN2 to the host cells.
Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation, and COE Program in the 21st century.
Chie
C
Aoki
Kazuya I P J
KI
Hidari
Saki
S
Itonori
Akihiro
A
Yamada
Naonori
N
Takahashi
Takeshi
T
Kasama
Futoshi
F
Hasebe
Mohammend Alimul
MA
Islam
Ken
K
Hatano
Koji
K
Matsuoka
Takao
T
Taki
Chao-Tan
CT
Guo
Tadanobu
T
Takahashi
Yuichi
Y
Sakano
Takashi
T
Suzuki
Daisei
D
Miyamoto
Mutsumi
M
Sugita
Daiyo
D
Terunuma
Koichi
K
Morita
Yasuo
Y
Suzuki
D000818:Animals; D001921:Brain / Q000378:metabolism; D002240:Carbohydrate Sequence; D002417:Cattle; D002460:Cell Line; D006224:Cricetinae; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism; D003716:Dengue Virus / Q000378:metabolism*; D006028:Glycosphingolipids / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D008969:Molecular Sequence Data
D050091:Dendrimers; D006028:Glycosphingolipids