Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

• DOI: 10.1371/journal.ppat.1002243
• Publication Date: 2011-09-01T21:44:47Z
• Authors: 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
• Keywords: Viral evolution; Viral quasispecies; Chronic infection; Sanger sequencing

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, also those drive progression to chronicity instrumental for understanding pathogenesis vaccine design. A comprehensive longitudinal analysis the population was conducted in four subjects followed from very early acute resolution disease outcome. By means next generation sequencing (NGS) standard cloning/Sanger sequencing, genetic diversity variants were quantified over course at frequencies as low 0.1%. Phylogenetic reassembled revealed dominated by two sequential bottleneck events, irrespective subsequent or clearance. first associated with transmission, one establishing infection. second occurred approximately 100 days post-infection, characterized decline diversity. In who developed this emergence new population, evolved founder via selective sweep fixation small number mutated sites. sites non-synonymous mutation higher predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide detailed within-host evolution HCV, indicating strong forces limit phase