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Link between the numbers of particles and variants founding new HIV-1 infections depends on the timing of transmission
Understanding which HIV-1 variants are most likely to be transmitted is important for vaccine design and predicting virus evolution. Since most infections are founded by single variants, it has been suggested that selection at transmission has a key role in governing which variants are transmitted....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354028/ https://www.ncbi.nlm.nih.gov/pubmed/30723550 http://dx.doi.org/10.1093/ve/vey038 |
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author | Thompson, Robin N Wymant, Chris Spriggs, Rebecca A Raghwani, Jayna Fraser, Christophe Lythgoe, Katrina A |
author_facet | Thompson, Robin N Wymant, Chris Spriggs, Rebecca A Raghwani, Jayna Fraser, Christophe Lythgoe, Katrina A |
author_sort | Thompson, Robin N |
collection | PubMed |
description | Understanding which HIV-1 variants are most likely to be transmitted is important for vaccine design and predicting virus evolution. Since most infections are founded by single variants, it has been suggested that selection at transmission has a key role in governing which variants are transmitted. We show that the composition of the viral population within the donor at the time of transmission is also important. To support this argument, we developed a probabilistic model describing HIV-1 transmission in an untreated population, and parameterised the model using both within-host next generation sequencing data and population-level epidemiological data on heterosexual transmission. The most basic HIV-1 transmission models cannot explain simultaneously the low probability of transmission and the non-negligible proportion of infections founded by multiple variants. In our model, transmission can only occur when environmental conditions are appropriate (e.g. abrasions are present in the genital tract of the potential recipient), allowing these observations to be reconciled. As well as reproducing features of transmission in real populations, our model demonstrates that, contrary to expectation, there is not a simple link between the number of viral variants and the number of viral particles founding each new infection. These quantities depend on the timing of transmission, and infections can be founded with small numbers of variants yet large numbers of particles. Including selection, or a bias towards early transmission (e.g. due to treatment), acts to enhance this conclusion. In addition, we find that infections initiated by multiple variants are most likely to have derived from donors with intermediate set-point viral loads, and not from individuals with high set-point viral loads as might be expected. We therefore emphasise the importance of considering viral diversity in donors, and the timings of transmissions, when trying to discern the complex factors governing single or multiple variant transmission. |
format | Online Article Text |
id | pubmed-6354028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63540282019-02-05 Link between the numbers of particles and variants founding new HIV-1 infections depends on the timing of transmission Thompson, Robin N Wymant, Chris Spriggs, Rebecca A Raghwani, Jayna Fraser, Christophe Lythgoe, Katrina A Virus Evol Research Article Understanding which HIV-1 variants are most likely to be transmitted is important for vaccine design and predicting virus evolution. Since most infections are founded by single variants, it has been suggested that selection at transmission has a key role in governing which variants are transmitted. We show that the composition of the viral population within the donor at the time of transmission is also important. To support this argument, we developed a probabilistic model describing HIV-1 transmission in an untreated population, and parameterised the model using both within-host next generation sequencing data and population-level epidemiological data on heterosexual transmission. The most basic HIV-1 transmission models cannot explain simultaneously the low probability of transmission and the non-negligible proportion of infections founded by multiple variants. In our model, transmission can only occur when environmental conditions are appropriate (e.g. abrasions are present in the genital tract of the potential recipient), allowing these observations to be reconciled. As well as reproducing features of transmission in real populations, our model demonstrates that, contrary to expectation, there is not a simple link between the number of viral variants and the number of viral particles founding each new infection. These quantities depend on the timing of transmission, and infections can be founded with small numbers of variants yet large numbers of particles. Including selection, or a bias towards early transmission (e.g. due to treatment), acts to enhance this conclusion. In addition, we find that infections initiated by multiple variants are most likely to have derived from donors with intermediate set-point viral loads, and not from individuals with high set-point viral loads as might be expected. We therefore emphasise the importance of considering viral diversity in donors, and the timings of transmissions, when trying to discern the complex factors governing single or multiple variant transmission. Oxford University Press 2019-01-30 /pmc/articles/PMC6354028/ /pubmed/30723550 http://dx.doi.org/10.1093/ve/vey038 Text en © The Author(s) 2019. Published by Oxford University Press. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Thompson, Robin N Wymant, Chris Spriggs, Rebecca A Raghwani, Jayna Fraser, Christophe Lythgoe, Katrina A Link between the numbers of particles and variants founding new HIV-1 infections depends on the timing of transmission |
title | Link between the numbers of particles and variants founding new HIV-1 infections depends on the timing of transmission |
title_full | Link between the numbers of particles and variants founding new HIV-1 infections depends on the timing of transmission |
title_fullStr | Link between the numbers of particles and variants founding new HIV-1 infections depends on the timing of transmission |
title_full_unstemmed | Link between the numbers of particles and variants founding new HIV-1 infections depends on the timing of transmission |
title_short | Link between the numbers of particles and variants founding new HIV-1 infections depends on the timing of transmission |
title_sort | link between the numbers of particles and variants founding new hiv-1 infections depends on the timing of transmission |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354028/ https://www.ncbi.nlm.nih.gov/pubmed/30723550 http://dx.doi.org/10.1093/ve/vey038 |
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