Branched oligosaccharide structures on HBV prevent interaction with both DC‐SIGN and L‐SIGN

Op den Brouw, M. L.; De Jong, M. A. W. P.; Ludwig, I. S.; Van Der Molen, R. G.; Janssen, H. L. A.; Geijtenbeek, T. B. H.; Woltman, A. M.

Summary. 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 α‐mannosidase I inhibitor kifunensine, is recognized by DC‐SIGN. The α‐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.