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 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.
|Keywords||DC-SIGN, Hepatitis B virus, L-SIGN, Viral recognition|
|Persistent URL||dx.doi.org/10.1111/j.1365-2893.2008.00993.x, hdl.handle.net/1765/30261|
|Journal||Journal of Viral Hepatitis|
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. (2008). Branched oligosaccharide structures on HBV prevent interaction with both DC-SIGN and L-SIGN. Journal of Viral Hepatitis, 15(9), 675–683. doi:10.1111/j.1365-2893.2008.00993.x