Mapping glycoprotein structure reveals defining events in the evolution of the Flaviviridae

Mifsud, J. C.O., Lytras, S., Oliver, M. R. , Toon, K. , Costa, V. A., Holmes, E. C. and Grove, J. (2024) Mapping glycoprotein structure reveals defining events in the evolution of the Flaviviridae. bioRxiv, (doi: 10.1101/2024.02.06.579159)

Abstract

Viral glycoproteins drive membrane fusion in enveloped viruses and determine host range, tissue tropism and pathogenesis. Despite their importance, there is a fragmentary understanding of glycoproteins within the Flaviviridae; for many species the glycoproteins have not yet been identified, for others, such as the hepaciviruses, the molecular mechanisms of membrane fusion remain uncharacterised. Here, we combine comprehensive phylogenetic analyses with systematic protein structure prediction to survey glycoproteins across the entire Flaviviridae. We discover class-II fusion systems, homologous to the orthoflavivirus E glycoprotein, in most species, including highly-divergent jingmenviruses and large genome flaviviruses. However, the E1E2 glycoproteins of the hepaci-, pegi- and pestiviruses are structurally distinct, may represent a novel class of fusion mechanism, and are strictly associated with infection of vertebrate hosts. By mapping glycoprotein distribution onto the underlying phylogeny we reveal a complex history of evolutionary events that have shaped the diverse virology and ecology of the Flaviviridae.

• Item Type: Articles (Pre-print)
• Additional Information: E.C.H. is supported by a National Health and Medical Research Council Investigator award (GNT2017197). J.C.O.M. is supported by the Australian Government’s Research Training Program Scholarship. J.G., S.L., and M.O. are supported by the Wellcome Trust and Royal Society through a Sir Henry Dale Fellowship (107653/Z/15/Z). K.T. was supported by a Lord Kelvin Adam Smith Fellowship from the University of Glasgow. J.G. is also supported by the MRC-University of Glasgow Centre for Virus Research core support from the Medical Research Council/UKRI (MC_UU_00034/1).
• Status: Published
• Refereed: No
• Glasgow Author(s) Enlighten ID: Grove, Dr Joe and Lytras, Mr Spyros and Toon, Dr Kamilla and Oliver, Dr Michael

Creator Roles

Lytras, S.: Methodology, Formal analysis, Investigation, Visualization, Writing – review and editing
Oliver, M.: Methodology, Writing – review and editing
Toon, K.: Methodology, Writing – review and editing
Grove, J.: Conceptualization, Methodology, Formal analysis, Visualization, Supervision, Funding acquisition, Writing – original draft, Writing – review and editing

• Authors: Mifsud, J. C.O., Lytras, S., Oliver, M. R., Toon, K., Costa, V. A., Holmes, E. C., and Grove, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: bioRxiv
• Copyright Holders: Copyright: © 2024 The Authors
• First Published: First published in BioRxiv 06 February 2024
• Publisher Policy: Reproduced under a Creative Commons licence
• Data DOI: 10.5281/zenodo.10616317