CD8+ T cell selection pressure is a major driving force for evolution of hepatitis C virus nonstructural proteins

Aims: Mutational escape from immune pressure exacted by CD8 T cells has been described during infection with hepatitis C virus (HCV). However, the extent to which this immune adaptation process contributes to viral evolution at the population level is less clear. Here, we took advantage of a large HCV genotype 1b outbreak after inoculation of contaminated immunoglobulins in 1977/78 to study this adaptation process. Methods: Samples were collected since 2008 and HLA-typed. The nonstructural protein coding regions NS3-NS5B were sequenced from 78 patients and mutations mapped according to their location inside or o…