Population genomics of louping ill virus provide new insights into the evolution of tick-borne flaviviruses

Clark, J. J., Gilray, J., Orton, R. J. , Baird, M., Wilkie, G., da Silva Filipe, A. , Johnson, N., McInnes, C. J., Kohl, A. and Biek, R. (2020) Population genomics of louping ill virus provide new insights into the evolution of tick-borne flaviviruses. PLoS Neglected Tropical Diseases, 14(9), e0008133. (doi: 10.1371/journal.pntd.0008133) (PMID:32925939) (PMCID:PMC7515184)

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Abstract

The emergence and spread of tick-borne arboviruses pose an increased challenge to human and animal health. In Europe this is demonstrated by the increasingly wide distribution of tick-borne encephalitis virus (TBEV, Flavivirus, Flaviviridae), which has recently been found in the United Kingdom (UK). However, much less is known about other tick-borne flaviviruses (TBFV), such as the closely related louping ill virus (LIV), an animal pathogen which is endemic to the UK and Ireland, but which has been detected in other parts of Europe including Scandinavia and Russia. The emergence and potential spatial overlap of these viruses necessitates improved understanding of LIV genomic diversity, geographic spread and evolutionary history. We sequenced a virus archive composed of 22 LIV isolates which had been sampled throughout the UK over a period of over 80 years. Combining this dataset with published virus sequences, we detected no sign of recombination and found low diversity and limited evidence for positive selection in the LIV genome. Phylogenetic analysis provided evidence of geographic clustering as well as long-distance movement, including movement events that appear recent. However, despite genomic data and an 80-year time span, we found that the data contained insufficient temporal signal to reliably estimate a molecular clock rate for LIV. Additional analyses revealed that this also applied to TBEV, albeit to a lesser extent, pointing to a general problem with phylogenetic dating for TBFV. The 22 LIV genomes generated during this study provide a more reliable LIV phylogeny, improving our knowledge of the evolution of tick-borne flaviviruses. Our inability to estimate a molecular clock rate for both LIV and TBEV suggests that temporal calibration of tick-borne flavivirus evolution should be interpreted with caution and highlight a unique aspect of these viruses which may be explained by their reliance on tick vectors.

Item Type:Articles
Additional Information:This work was also supported by the UK Medical Research Council with grant MC_UU_12014/12).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilkie, Dr Gavin and Biek, Professor Roman and Baird, Mrs Margaret and Da Silva Filipe, Dr Ana and Kohl, Professor Alain and CLARK, Jordan and Orton, Dr Richard
Creator Roles:
Clark, J. J.Data curation, Formal analysis, Investigation, Methodology, Validation, Writing – original draft, Writing – review and editing
Orton, R. J.Resources, Writing – review and editing
Baird, M.Resources
Wilkie, G.Resources
da Silva Filipe, A.Resources, Writing – review and editing
Kohl, A.Conceptualization, Funding acquisition, Supervision, Writing – review and editing
Biek, R.Conceptualization, Formal analysis, Funding acquisition, Methodology, Supervision, Validation, Writing – original draft, Writing – review and editing
Authors: Clark, J. J., Gilray, J., Orton, R. J., Baird, M., Wilkie, G., da Silva Filipe, A., Johnson, N., McInnes, C. J., Kohl, A., and Biek, R.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2020 Clark et al.
First Published:First published in PLoS Neglected Tropical Diseases 14(9): e0008133
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190659BBSRC Doctoral Training Partnership 2012Jeremy MottramBiotechnology and Biological Sciences Research Council (BBSRC)BB/J013854/1MVLS - Graduate School
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH