Identifying the genetic basis of viral spillover using Lassa virus as a test case

Whitlock, A. O. B. et al. (2023) Identifying the genetic basis of viral spillover using Lassa virus as a test case. Royal Society Open Science, 10(3), 221503. (doi: 10.1098/rsos.221503) (PMID:36968239) (PMCID:PMC10031424)

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The rate at which zoonotic viruses spill over into the human population varies significantly over space and time. Remarkably, we do not yet know how much of this variation is attributable to genetic variation within viral populations. This gap in understanding arises because we lack methods of genetic analysis that can be easily applied to zoonotic viruses, where the number of available viral sequences is often limited, and opportunistic sampling introduces significant population stratification. Here, we explore the feasibility of using patterns of shared ancestry to correct for population stratification, enabling genome-wide association methods to identify genetic substitutions associated with spillover into the human population. Using a combination of phylogenetically structured simulations and Lassa virus sequences collected from humans and rodents in Sierra Leone, we demonstrate that existing methods do not fully correct for stratification, leading to elevated error rates. We also demonstrate, however, that the Type I error rate can be substantially reduced by confining the analysis to a less-stratified region of the phylogeny, even in an already-small dataset. Using this method, we detect two candidate single-nucleotide polymorphisms associated with spillover in the Lassa virus polymerase gene and provide generalized recommendations for the collection and analysis of zoonotic viruses.

Item Type:Articles
Additional Information:This work was supported by NIH R01GM122079 (to S.L.N.) and DARPA D18AC00028 (to B.H.B. and S.L.N.).
Keywords:Genome-wide association studies, Lassa virus, zoonosis, single-nucleotide polymorphisms, spillover, host shift.
Glasgow Author(s) Enlighten ID:Hughes, Dr Joseph and Vucak, Mr Matej and Nichols, Mrs Jenna and Davison, Professor Andrew
Authors: Whitlock, A. O. B., Bird, B. H., Ghersi, B., Davison, A. J., Hughes, J., Nichols, J., Vučak, M., Amara, E., Bangura, J., Lavalie, E. G., Kanu, M. C., Kanu, O. T., Sjodin, A., Remien, C. H., and Nuismer, S. L.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
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
Journal Name:Royal Society Open Science
Publisher:The Royal Society
ISSN (Online):2054-5703
Published Online:22 March 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Royal Society Open Science 10(3): 221503
Publisher Policy:Reproduced under a Creative Commons License
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