Lattova et al. Comprehensive N-glycosylation mapping of envelope glycoprotein from tick-borne encephalitis virus grown in human and tick cells.
Sci Rep. 2020 Aug 6;10(1):13204. doi: 10.1038/s41598-020-70082-2.
N-Glycans on viral proteins play essential roles in replication, immunogenicity, and pathogenicity. In the case of TBEV, N-glycosylation plays an important role in proper conformation of the envelope (E) protein during secretion in mammalian cells. On the other hand, the TBEV secretory/maturation process in tick cells seems to be independent of E protein N-glycosylation.
In this regard, the profile of N-glycans linked to the E protein of TBEV when grown in human neuronal cells was analyzed and compared to the profile of virus grown in tick cells. Mass spectrometric analysis revealed significant differences in these profiles. High-mannose glycan with five mannose residues (Man5GlcNAc2), a complex biantennary galactosylated structure with core fucose (Gal2GlcNAc2Man3GlcNAc2Fuc), and a group of hybrid glycans with the composition Gal0-1GlcNAc1Man3-5GlcNAc2Fuc0-1 were confirmed as the main asparagine-linked oligosaccharides on the surface of TBEV derived from human neuronal cells. The observed pattern was supported by examination of the glycopeptides, providing additional information about the glycosylation site in the E protein. In contrast, the profile of TBEV grown in tick cells showed that paucimannose (Man3-4 GlcNAc2Fuc0-1) and high-mannose structures with five and six mannoses (Man5-6GlcNAc2) were major glycans on the viral surface.
This study provides comprehensive mapping of the glycosylation on the TBEV E glycoprotein when the same virus type is grown in human and tick cells. The results expand existing crystallography data on the E glycoprotein. Furthermore, the data provide evidence that the N-glycan profile of TBEV E glycoprotein depends strongly on the host cell type. As proteins that bind to N-linked glycans of enveloped viruses represent a new emerging class of highly effective antivirals, our results might be useful in research for development of carbohydrate-binding agents as potential inhibitors of TBEV.
Author: Daniel Ruzek
Daniel Ruzek is a Head of the Laboratory of Arbovirology, Institute of Parasitology of the Czech Academy of Sciences, Ceske Budejovice, and Head of the Laboratory of Emerging Viral Infections, Veterinary Research Institute, Brno, Czech Republic. His research focuses on molecular biology of arboviruses, in particular tick-borne encephalitis virus (TBEV), and pathogenesis and the immune system response that controls TBEV and other arboviral infections. He works also on the development and testing of novel antivirals and vaccines effective against arboviruses.