The contribution of viral genotype to plasma viral set-point in HIV infection.

Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, usi...

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Autores principales:	Emma Hodcroft, Jarrod D Hadfield, Esther Fearnhill, Andrew Phillips, David Dunn, Siobhan O'Shea, Deenan Pillay, Andrew J Leigh Brown, UK HIV Drug Resistance Database, UK CHIC Study
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7ae06fb121e04d7289ac1c7d9c4dc792
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spelling	oai:doaj.org-article:7ae06fb121e04d7289ac1c7d9c4dc7922021-11-18T06:06:38ZThe contribution of viral genotype to plasma viral set-point in HIV infection.1553-73661553-737410.1371/journal.ppat.1004112https://doaj.org/article/7ae06fb121e04d7289ac1c7d9c4dc7922014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24789308/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8-8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms.Emma HodcroftJarrod D HadfieldEsther FearnhillAndrew PhillipsDavid DunnSiobhan O'SheaDeenan PillayAndrew J Leigh BrownUK HIV Drug Resistance DatabaseUK CHIC StudyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 5, p e1004112 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Emma Hodcroft Jarrod D Hadfield Esther Fearnhill Andrew Phillips David Dunn Siobhan O'Shea Deenan Pillay Andrew J Leigh Brown UK HIV Drug Resistance Database UK CHIC Study The contribution of viral genotype to plasma viral set-point in HIV infection.
description	Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8-8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms.
format	article
author	Emma Hodcroft Jarrod D Hadfield Esther Fearnhill Andrew Phillips David Dunn Siobhan O'Shea Deenan Pillay Andrew J Leigh Brown UK HIV Drug Resistance Database UK CHIC Study
author_facet	Emma Hodcroft Jarrod D Hadfield Esther Fearnhill Andrew Phillips David Dunn Siobhan O'Shea Deenan Pillay Andrew J Leigh Brown UK HIV Drug Resistance Database UK CHIC Study
author_sort	Emma Hodcroft
title	The contribution of viral genotype to plasma viral set-point in HIV infection.
title_short	The contribution of viral genotype to plasma viral set-point in HIV infection.
title_full	The contribution of viral genotype to plasma viral set-point in HIV infection.
title_fullStr	The contribution of viral genotype to plasma viral set-point in HIV infection.
title_full_unstemmed	The contribution of viral genotype to plasma viral set-point in HIV infection.
title_sort	contribution of viral genotype to plasma viral set-point in hiv infection.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7ae06fb121e04d7289ac1c7d9c4dc792
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The contribution of viral genotype to plasma viral set-point in HIV infection.

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