Branched oligosaccharide structures on HBV prevent interaction with both DC-SIGN and L-SIGN.
Hepatitis B virus (HBV) is a DNA virus that infects the liver as primary target. Currently, a high affinity receptor for HBV is still unknown. The dendritic cell specific C-type lectin DC-SIGN is involved in pathogen recognition through mannose and fucose containing carbohydrates leading to the induction of an anti-viral immune response. Many glycosylated viruses subvert this immune surveillance function and exploit DC-SIGN as a port of entry and for trans-infection of target cells. The glycosylation pattern on HBV surface antigens (HBsAg) together with the tissue distribution of HBV would allow interaction between HBV and DC-SIGN and its liver-expressed homologue L-SIGN. Therefore, a detailed study to investigate the binding of HBV to DC-SIGN and L-SIGN was performed. For HCV, both DC-SIGN and L-SIGN are known to bind envelope glycoproteins E1 and E2. Soluble DC-SIGN and L-SIGN specifically bound HCV virus-like particles, but no interaction with either HBsAg or HepG2.2.15-derived HBV was detected. Also, neither DC-SIGN nor L-SIGN transfected Raji cells bound HBsAg. In contrast, highly mannosylated HBV, obtained by treating HBV producing HepG2.2.15 cells with the alpha-mannosidase I inhibitor kifunensine, is recognized by DC-SIGN. The alpha-mannosidase I trimming of N-linked oligosaccharide structures thus prevents recognition by DC-SIGN. On the basis of these findings, it is tempting to speculate that HBV exploits mannose trimming as a way to escape recognition by DC-SIGN and thereby subvert a possible immune activation response.
Op den Brouw
M L
ML
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands.
de Jong
M A W P
MA
Ludwig
I S
IS
van der Molen
R G
RG
Janssen
H L A
HL
Geijtenbeek
T B H
TB
Woltman
A M
AM
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D025942:Oligosaccharides, Branched-Chain / Q000032:analysis* / Q000276:immunology*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D053585:Virus Attachment; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D006514:Hepatitis B Surface Antigens; D037181:Lectins, C-Type; D025942:Oligosaccharides, Branched-Chain; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human