Variation in physicochemical properties of the hypervariable region 1 during acute and chronic stages of hepatitis C virus infection

Differentiation between acute and chronic HCV infections is clinically important given that early treatment of infected patients leads to high rates of sustained virological response. Analysis of HVR1 sequences (n=2179) from samples obtained from patients with acute (n=49) and chronic (n=102) HCV infections showed that intra-host HVR1 diversity was 1.8 times higher in patients with chronic than acute infection. Analysis of molecular variance showed significant differences between sequences from acute and chronic patients. We found statistically significant differences in polarity, volume and hydrophobicity of amino acids at 10 HVR1 positions. A classification model constructed using the 10 positions in HVR1 distinguished between acute and chronic cases with accuracy of 88% in cross-validation experiments. The results indicate that progression from acute to chronic stage of HCV infection is accompanied by characteristic changes in amino acid composition of HVR1, suggesting a substantial regularity of the intra-host HVR1 evolution.