N-Glycosylation and N-Glycan Processing in HBV Biology and Pathogenesis

Abstract

Hepatitis B Virus (HBV) glycobiology has been an area of intensive research in the last decades and continues to be an attractive topic due to the multiple roles that N-glycosylation in particular plays in the virus life-cycle and its interaction with the host that are still being discovered. The three HBV envelope glycoproteins, small (S), medium (M) and large (L) share a very peculiar N-glycosylation pattern, which distinctly regulates their folding, degradation, assembly, intracellular trafficking and antigenic properties. In addition, recent findings indicate important roles of N-linked oligosaccharides in viral pathogenesis and evasion of the immune system surveillance. This review focuses on N-glycosylation’s contribution to HBV infection and disease, with implications for development of improved vaccines and antiviral therapies.

Pathogenicity and virulence of Hepatitis B virus

“…The N-terminal two TM segments contain two topogenic signals for their proper positioning in the lipid bilayer[ 162 ]. These three envelope proteins share an N-linked glycosylation site at asparagine-146 (Asn-146) in the luminal loop[ 163 ]. This glycosylation site is only partially used, resulting in the generation of both glycosylated and non-glycosylated forms of surface proteins[ 164 ].…”

Mutations in the envelope protein associated with hepatitis B virus reactivation

“…Recently, the clinical importance of additional N ‐linked glycosylation mutations were reported in patients with HBVr, 10,11 those who were HBsAg and anti‐HBs double‐positive, 12 and patients with hepatocellular carcinoma 13 . A previous review article described the importance of N ‐glycosylation and N ‐glycan processing in HBV biology and pathogenesis 14 . In the current case, additional N ‐linked glycosylation mutations were not detected by direct sequencing.…”

Association of the Hepatitis B Virus Large Surface Protein with Viral Infectivity and Endoplasmic Reticulum Stress-mediated Liver Carcinogenesis

“…The N-terminal pre-S regions have unique protein conformations that protrude from the endoplasmic reticulum (ER) membrane and lead to specific interplay between viral medium/large surface and host proteins, in addition to their roles as integral proteins in the virus envelope [ 14 ]. Glycosylation reactions have been documented to regulate the protein topologies of surface proteins, which are mainly incorporated across the cell and ER membranes [ 15 ] ( Figure 1 ).…”