Lack of variant specific CD8+T-cell response against mutant and pre-existing variants leads to outgrowth of particular clones in acute hepatitis C

Background: CTL escape mutations have been described during acute
hepatitis C in patients who developed chronic disease later on. Our
aim was to investigate the mutual relationship between HCV specific
CD8+ T cells and evolution of the viral sequence during early acute
HCV infection. Results: We sequenced multiple clones of NS3 1406
epitope in 4 HLA-A{*}02 patients with acute hepatitis C genotype 1b
infection. Pentamers specific for the variants were used to monitor
the corresponding CD8+ T cell response. We observed outgrowth of
mutations, which induced only a weak and thus potentially
insufficient CD8+ T cell response. In one patient we observed
outgrowth of variant epitopes with similarities to a different
genotype rather than de novo mutations most probably due to a lack
of responsiveness to these likely pre-existing variants. We could
show that in acute hepatitis C CTL escape mutations occur much
earlier than demonstrated in previous studies. Conclusions: The
adaption of the virus to a new host is characterized by a high and
rapid variability in epitopes under CD8+ T cell immune pressure.
This adaption takes place during the very early phase of acute
infection and strikingly some sequences were reduced below the
limit of detection at some time points but were detected at high
frequency again at later time points. Independent of the observed
variability, HCV-specific CD8+ T cell responses decline and no
adaption to different or new antigens during the course of
infection could be detected.