Ghafari, M., Lumby, C. K., Weissman, D. B. and Illingworth, C. J. R. (2020) Inferring transmission bottleneck size from viral sequence data using a novel haplotype reconstruction method. Journal of Virology, 94(13), e00014-20. (doi: 10.1128/JVI.00014-20) (PMID:32295920) (PMCID:PMC7307158)
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Abstract
The transmission bottleneck is defined as the number of viral particles that transmit from one host to establish an infection in another. Genome sequence data have been used to evaluate the size of the transmission bottleneck between humans infected with the influenza virus; however, the methods used to make these estimates have some limitations. Specifically, viral allele frequencies, which form the basis of many calculations, may not fully capture a process which involves the transmission of entire viral genomes. Here, we set out a novel approach for inferring viral transmission bottlenecks; our method combines an algorithm for haplotype reconstruction with maximum likelihood methods for bottleneck inference. This approach allows for rapid calculation and performs well when applied to data from simulated transmission events; errors in the haplotype reconstruction step did not adversely affect inferences of the population bottleneck. Applied to data from a previous household transmission study of influenza A infection, we confirm the result that the majority of transmission events involve a small number of viruses, albeit with slightly looser bottlenecks being inferred, with between 1 and 13 particles transmitted in the majority of cases. While influenza A transmission involves a tight population bottleneck, the bottleneck is not so tight as to universally prevent the transmission of within-host viral diversity.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust (wellcome.ac.uk) and the Royal Society (royalsociety.org) with grant number 101239/Z/13/Z. C.K.L. was funded by a Wellcome Trust studentship with grant number 105365/Z/14/Z. C.J.R.I. acknowledges a visiting fellowship from the University of Helsinki. D.B.W. was funded by a Simons Investigator award from the Simons Foundation with grant number 508600. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Illingworth, Dr Chris |
| Authors: | Ghafari, M., Lumby, C. K., Weissman, D. B., and Illingworth, C. J. 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 |
| Journal Name: | Journal of Virology |
| Publisher: | American Society for Microbiology |
| ISSN: | 0022-538X |
| ISSN (Online): | 1098-5514 |
| Published Online: | 15 April 2020 |
| Copyright Holders: | Copyright © 2020 Ghafari et al. |
| First Published: | First published in Journal of Virology 94(13): e00014-20 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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