Acute infection with a single hepatitis C virus strain in dialysis patients: Analysis of adaptive immune response and viral variability☆

Background/Aims

While the adaptive immune response is crucial for spontaneous resolution of acute hepatitis C virus (HCV) infection, it also constitutes the driving force for viral escape. For acutely HCV-infected dialysis patients, little is known about the host response and its impact on viral evolution.

Methods

Four haemodialysis patients accidentally infected with the same HCV strain were prospectively investigated with respect to the clinical course, CD4+ and CD8+ T-cell responses, neutralizing antibodies, viral kinetics and sequence variability.

Results

In one patient, a robust CD4+ T-cell response was associated with transient control of infection, while in the other patients, weak responses correlated with persistently high viremia. Despite the presence of CD8+ T-cell effectors in the first patient, no sequence differences were detected in targeted regions of the viral genome in any of the patients when viral persistence was established. Genetic stability in the envelope genes, including the hypervariable regions, correlated with low-level or absent neutralizing antibodies in all of the patients.

Conclusions

The establishment of viral persistence in the special patient group of dialysis patients is due to a failure of the adaptive immune system, as shown by the absence of significant T-cell and antibody responses, as well as viral variability.

Abbreviations: HCV, hepatitis C virus, TH1, T-helper cells type 1, RNA, ribonucleic acid, HVR1, hypervariable region 1, ELISA, enzyme linked immuno sorbent assay, PCR, polymerase chain reaction, NS3, non structural protein 3, NS4, non structural protein 4, IFN-gamma, interferon-gamma, TNF-alpha, tumor necrosis factor-alpha, SD, standard deviation, PBMC, peripheral blood mononuclear cells, HCVpp, HCV pseudotype particles, GFP, green fluorescent protein, PE, post exposure, LC, local controls, ALT, alanine aminotransferase, HLA, human leukocyte antigen, HVR2, hypervariable region 2

Keywords: Hepatitis C virus, Acute hepatitis C, Dialysis, T-cells, Neutralizing antibodies, Virus host interaction, CD4, CD8, Immune response, Viral variability