Journal article
Sequential bottlenecks drive viral evolution in early acute Hepatitis C virus infection
PLoS Pathogens, Vol.7(9), e1002243
2011
Abstract
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.
Details
- Title
- Sequential bottlenecks drive viral evolution in early acute Hepatitis C virus infection
- Authors/Creators
- R.A. Bull (Author/Creator)F. Luciani (Author/Creator)K. McElroy (Author/Creator)S. Gaudieri (Author/Creator)S.T. Pham (Author/Creator)A. Chopra (Author/Creator)B. Cameron (Author/Creator)L. Maher (Author/Creator)G.J. Dore (Author/Creator)P.A. White (Author/Creator)A.R. Lloyd (Author/Creator)
- Publication Details
- PLoS Pathogens, Vol.7(9), e1002243
- Publisher
- Public Library of Science
- Identifiers
- 991005543928507891
- Copyright
- Bull et al. 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 credited.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.125 Hepatitis
- 1.125.83 HCV
- Web Of Science research areas
- Microbiology
- Parasitology
- Virology
- ESI research areas
- Microbiology