Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design....

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Autores principales:	Rowena A Bull, Fabio Luciani, Kerensa McElroy, Silvana Gaudieri, Son T Pham, Abha Chopra, Barbara Cameron, Lisa Maher, Gregory J Dore, Peter A White, Andrew R Lloyd
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/77f43060385246b091694300039a2d3e
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spelling	oai:doaj.org-article:77f43060385246b091694300039a2d3e2021-11-18T06:03:00ZSequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.1553-73661553-737410.1371/journal.ppat.1002243https://doaj.org/article/77f43060385246b091694300039a2d3e2011-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21912520/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection.Rowena A BullFabio LucianiKerensa McElroySilvana GaudieriSon T PhamAbha ChopraBarbara CameronLisa MaherGregory J DorePeter A WhiteAndrew R LloydPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 9, p e1002243 (2011)
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 Rowena A Bull Fabio Luciani Kerensa McElroy Silvana Gaudieri Son T Pham Abha Chopra Barbara Cameron Lisa Maher Gregory J Dore Peter A White Andrew R Lloyd Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.
description	Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection.
format	article
author	Rowena A Bull Fabio Luciani Kerensa McElroy Silvana Gaudieri Son T Pham Abha Chopra Barbara Cameron Lisa Maher Gregory J Dore Peter A White Andrew R Lloyd
author_facet	Rowena A Bull Fabio Luciani Kerensa McElroy Silvana Gaudieri Son T Pham Abha Chopra Barbara Cameron Lisa Maher Gregory J Dore Peter A White Andrew R Lloyd
author_sort	Rowena A Bull
title	Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.
title_short	Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.
title_full	Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.
title_fullStr	Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.
title_full_unstemmed	Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.
title_sort	sequential bottlenecks drive viral evolution in early acute hepatitis c virus infection.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/77f43060385246b091694300039a2d3e
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Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.

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