Cargando…

Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach

Recent data shows that HIV-1 is characterised by variation in viral virulence factors that is heritable between infections, which suggests that viral virulence can be naturally selected at the population level. A trade-off between transmissibility and duration of infection appears to favour viruses...

Descripción completa

Detalles Bibliográficos
Autores principales: Shirreff, George, Pellis, Lorenzo, Laeyendecker, Oliver, Fraser, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192807/
https://www.ncbi.nlm.nih.gov/pubmed/22022243
http://dx.doi.org/10.1371/journal.pcbi.1002185
_version_ 1782213800142831616
author Shirreff, George
Pellis, Lorenzo
Laeyendecker, Oliver
Fraser, Christophe
author_facet Shirreff, George
Pellis, Lorenzo
Laeyendecker, Oliver
Fraser, Christophe
author_sort Shirreff, George
collection PubMed
description Recent data shows that HIV-1 is characterised by variation in viral virulence factors that is heritable between infections, which suggests that viral virulence can be naturally selected at the population level. A trade-off between transmissibility and duration of infection appears to favour viruses of intermediate virulence. We developed a mathematical model to simulate the dynamics of putative viral genotypes that differ in their virulence. As a proxy for virulence, we use set-point viral load (SPVL), which is the steady density of viral particles in blood during asymptomatic infection. Mutation, the dependency of survival and transmissibility on SPVL, and host effects were incorporated into the model. The model was fitted to data to estimate unknown parameters, and was found to fit existing data well. The maximum likelihood estimates of the parameters produced a model in which SPVL converged from any initial conditions to observed values within 100–150 years of first emergence of HIV-1. We estimated the 1) host effect and 2) the extent to which the viral virulence genotype mutates from one infection to the next, and found a trade-off between these two parameters in explaining the variation in SPVL. The model confirms that evolution of virulence towards intermediate levels is sufficiently rapid for it to have happened in the early stages of the HIV epidemic, and confirms that existing viral loads are nearly optimal given the assumed constraints on evolution. The model provides a useful framework under which to examine the future evolution of HIV-1 virulence.
format Online
Article
Text
id pubmed-3192807
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-31928072011-10-21 Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach Shirreff, George Pellis, Lorenzo Laeyendecker, Oliver Fraser, Christophe PLoS Comput Biol Research Article Recent data shows that HIV-1 is characterised by variation in viral virulence factors that is heritable between infections, which suggests that viral virulence can be naturally selected at the population level. A trade-off between transmissibility and duration of infection appears to favour viruses of intermediate virulence. We developed a mathematical model to simulate the dynamics of putative viral genotypes that differ in their virulence. As a proxy for virulence, we use set-point viral load (SPVL), which is the steady density of viral particles in blood during asymptomatic infection. Mutation, the dependency of survival and transmissibility on SPVL, and host effects were incorporated into the model. The model was fitted to data to estimate unknown parameters, and was found to fit existing data well. The maximum likelihood estimates of the parameters produced a model in which SPVL converged from any initial conditions to observed values within 100–150 years of first emergence of HIV-1. We estimated the 1) host effect and 2) the extent to which the viral virulence genotype mutates from one infection to the next, and found a trade-off between these two parameters in explaining the variation in SPVL. The model confirms that evolution of virulence towards intermediate levels is sufficiently rapid for it to have happened in the early stages of the HIV epidemic, and confirms that existing viral loads are nearly optimal given the assumed constraints on evolution. The model provides a useful framework under which to examine the future evolution of HIV-1 virulence. Public Library of Science 2011-10-13 /pmc/articles/PMC3192807/ /pubmed/22022243 http://dx.doi.org/10.1371/journal.pcbi.1002185 Text en Shirreff et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shirreff, George
Pellis, Lorenzo
Laeyendecker, Oliver
Fraser, Christophe
Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach
title Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach
title_full Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach
title_fullStr Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach
title_full_unstemmed Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach
title_short Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach
title_sort transmission selects for hiv-1 strains of intermediate virulence: a modelling approach
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192807/
https://www.ncbi.nlm.nih.gov/pubmed/22022243
http://dx.doi.org/10.1371/journal.pcbi.1002185
work_keys_str_mv AT shirreffgeorge transmissionselectsforhiv1strainsofintermediatevirulenceamodellingapproach
AT pellislorenzo transmissionselectsforhiv1strainsofintermediatevirulenceamodellingapproach
AT laeyendeckeroliver transmissionselectsforhiv1strainsofintermediatevirulenceamodellingapproach
AT fraserchristophe transmissionselectsforhiv1strainsofintermediatevirulenceamodellingapproach