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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: Bull, Rowena A., Luciani, Fabio, McElroy, Kerensa, Gaudieri, Silvana, Pham, Son T., Chopra, Abha, Cameron, Barbara, Maher, Lisa, Dore, Gregory J., White, Peter A., Lloyd, Andrew R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164670/
https://www.ncbi.nlm.nih.gov/pubmed/21912520
http://dx.doi.org/10.1371/journal.ppat.1002243
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author Bull, Rowena A.
Luciani, Fabio
McElroy, Kerensa
Gaudieri, Silvana
Pham, Son T.
Chopra, Abha
Cameron, Barbara
Maher, Lisa
Dore, Gregory J.
White, Peter A.
Lloyd, Andrew R.
author_facet Bull, Rowena A.
Luciani, Fabio
McElroy, Kerensa
Gaudieri, Silvana
Pham, Son T.
Chopra, Abha
Cameron, Barbara
Maher, Lisa
Dore, Gregory J.
White, Peter A.
Lloyd, Andrew R.
author_sort Bull, Rowena A.
collection PubMed
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.
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spelling pubmed-31646702011-09-12 Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection Bull, Rowena A. Luciani, Fabio McElroy, Kerensa Gaudieri, Silvana Pham, Son T. Chopra, Abha Cameron, Barbara Maher, Lisa Dore, Gregory J. White, Peter A. Lloyd, Andrew R. PLoS Pathog Research Article 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. Public Library of Science 2011-09-01 /pmc/articles/PMC3164670/ /pubmed/21912520 http://dx.doi.org/10.1371/journal.ppat.1002243 Text en Bull 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
Bull, Rowena A.
Luciani, Fabio
McElroy, Kerensa
Gaudieri, Silvana
Pham, Son T.
Chopra, Abha
Cameron, Barbara
Maher, Lisa
Dore, Gregory J.
White, Peter A.
Lloyd, Andrew R.
Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164670/
https://www.ncbi.nlm.nih.gov/pubmed/21912520
http://dx.doi.org/10.1371/journal.ppat.1002243
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