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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....

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Autores principales: Thompson, Robin N, Wymant, Chris, Spriggs, Rebecca A, Raghwani, Jayna, Fraser, Christophe, Lythgoe, Katrina A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
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.
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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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