Estimating viral bottleneck sizes for FMDV transmission within and between hosts and implications for the rate of viral evolution

Orton, R. J. , Wright, C. F., King, D. P. and Haydon, D. T. (2020) Estimating viral bottleneck sizes for FMDV transmission within and between hosts and implications for the rate of viral evolution. Interface Focus, 10, 20190066. (doi: 10.1098/rsfs.2019.0066) (PMID:31897294) (PMCID:PMC6936012)

[img]
Preview
Text
201919.pdf - Accepted Version
Available under License Creative Commons Attribution.

740kB

Abstract

RNA viruses exist as populations of closely related genomes, characterized by a high diversity of low-frequency variants. As viral genomes from one population disperse to establish new sites of replication, the fate of these low-frequency variants depends to a large extent on the size of the founding population. Focusing on foot-and-mouth disease virus (FMDV) we conjecture that variants are more likely to be transmitted through wide bottlenecks, but more likely to approach fixation in new populations following narrow bottlenecks; therefore, the longer-term rate of accumulation of ‘nearly neutral’ variants at high frequencies is likely to be inversely related to the bottleneck size. We examine this conjecture in vivo by estimating bottleneck sizes relating ‘parent’ and ‘daughter’ populations observed at different scales ranging from within host to between host (within the same herd, and in different herds) using a previously established method. Within hosts, we find bottleneck sizes to range from 5 to 20 viral genomes between populations transmitted from the pharynx to the serum, and from 4 to 54 between serum and lesion populations. Between hosts, we find bottleneck sizes to range from 2 to 39, suggesting inter-host bottlenecks are of a similar size to intra-host bottlenecks. We establish a statistically significant negative relationship between the probability of genomic consensus level change and bottleneck size, and present a simple sampling model that captures this empirical relationship. We also present a novel in vitro experiment to investigate the impact of bottleneck size on the frequency of mutations within FMDV populations, demonstrate that variant frequency in a population increases more rapidly during small population passages, and provide evidence for positive selection during the passage of large populations.

Item Type:Articles
Additional Information:Work undertaken at The Pirbright Institute was supported by the Biotechnology and Biological Sciences Research Council of the United Kingdom (projects BBS/E/I/00007035 and BBS/E/I/00007036). Work undertaken at the University of Glasgow was supported by the Biotechnology and Biological Sciences Research Council, UK via a DTA PhD studentship (project BB/E018505/1) and BBSRC standard grant (projects BB/I013784/1 and BB/I014314/1). R.J.O. is currently funded by the Medical Research Council (MC_UU_12014/12).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:King, Dr Donald and Haydon, Professor Daniel and Orton, Dr Richard
Authors: Orton, R. J., Wright, C. F., King, D. P., and Haydon, D. T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Interface Focus
Publisher:The Royal Society
ISSN:2042-8901
ISSN (Online):2042-8901
Published Online:13 December 2019
Copyright Holders:Copyright © 2019 The Author(s)
First Published:First published in Interface Focus
Publisher Policy:Reproduced in accordance with the publisher copyright policy

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
142269Population genetics and genomics of ovine parasitic nematodes and their application to the study of anthelmintic resistanceAndrew TaitBiotechnology and Biological Sciences Research Council (BBSRC)BB/E018505/1III - Bacteriology
165375Beyond the consensus dissecting viral sequence diversity within samplesRichard OrtonBiotechnology and Biological Sciences Research Council (BBSRC)BB/I013784/1Institute of Biodiversity, Animal Health and Comparative Medicine