Virus glycosylation: role in virulence and immune interactions

Abstract

The study of N-linked glycosylation as it relates to virus biology has become an area of intense interest in recent years due to its ability to impart various advantages to virus survival and virulence. HIV and influenza, two clear threats to human health, have been shown to rely on expression of specific oligosaccharides to evade detection by the host immune system. Additionally, other viruses such as Hendra, SARS-CoV, influenza, hepatitis and West Nile rely on N-linked glycosylation for crucial functions such as entry into host cells, proteolytic processing and protein trafficking. This review focuses on recent findings on the importance of glycosylation to viral virulence and immune evasion for several prominent human pathogens.

Figure 1

Biosynthetic pathway for the generation of N-linked glycosylation. Processing of N-linked oligosaccharide occurs in the ER and Golgi. Following glucose trimming in the ER, high mannose glycans are available for further processing and trimming by glycosidase and mannosidases to yield high-mannose, hybrid and complex glycan structures.

Figure 2

Glycan interactions result in virus neutralization, internalization or degradation. Interactions between virus envelope glycoprotein and host molecules comprise several general interactions. (a) Virus glycan can interact with cell-surface-bound lectin molecules such as MMR and DC-SIGN to obtain entry into the target cell. (b) Lectin binding to virus can lead to internalization of complexed virus into a degradative pathway for processing and presentation to the immune system. (c) Soluble lectin such as SP-D or MMR can interact with virus glycans to neutralize virus infectivity and block associations with host cell receptors.