The only exception found of a variation in HLA non-restricted epitopes (NS3 1359�C67, sellckchem NS3 1382�C97) in patient 2 can be either explained by pre-existing different strains or, in the absence of ongoing selecting immune pressure, reversion of a mutation to a more favourable sequence for the virus with respect to viral replication. Our findings indicate that the virus is very stable without immune pressure. Future longitudinal analysis of the whole genome during the early phase of acute infection should elucidate the hot spots like NS3 1406 epitope. A better understanding of these hot spots could be of outstanding importance for a vaccine development. Conclusions In summary, we demonstrated that CTL escape mutations occur much earlier than previously demonstrated in acute HCV infection.

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. Variants can drop below the limit of detection during the course of infection and reappear at later time points. Most strikingly, HCV-specific CD8+ T cell responses induced very early during infection seem to be unable to adapt to different or new antigens during the course of infection. Independent of the variability, the CD8+ T cell response is not sustained sufficiently. This phenomenon indicates that different complementary mechanisms are active in acute hepatitis C. Epitopes under immune pressure evade by mutations but can reoccur while the CD8+ response is already vanishing.

A better understanding of this peculiar silencing of the CD8+ T cell response, which seems to be one of the hallmarks of acute hepatitis C, could be critical in further elucidating the pathogenesis of the chronic phase of the disease. Methods Patients In this study the following patients were included: 4 patients with acute hepatitis C infection. Time point zero was defined as onset of symptoms and diagnosis of acute HCV infection. Acute hepatitis C was diagnosed by documented seroconversion to anti-HCV antibodies or all of the following: acute onset of hepatitis in previously healthy GSK-3 individual, aminotransferases at least 10�� the upper limit of normal, exclusion of other infectious, metabolic, or toxic causes of hepatitis, recent exposure or source of infection identified. At different time points during the course of disease patient 1, 3 and 4 received antiviral treatment with subsequent viral elimination. Patient 2 did not receive antiviral treatment. For further clinical characteristics of the patients see Table 1. Further inclusion criteria were HLA-A0201 genotype and positive tetramer staining with the NS3 1406�C1415 index pentamer.