Variations in the core region of hepatitis C virus genomes in patients with chronic hepatitis

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Abstract
In each infected patient, the population of hepatitis C virus is composed of quasispecies that differ in their nucleotide sequences. Among regions in hepatitis C virus genomes, nucleotide sequences of the hypervariable region have been shown to change quickly during the course of infection. It is not known, however, whether these variations exist in the core region that has recently been suggested to contain human lymphocyte antigen class 1 restricted sites for cytotoxic T cell recognition. To clarify this, RNA was extracted from the plasma of four patients with chronic hepatitis C. After cDNA synthesis, DNA fragments that contain the core region were amplified by the polymerase chain reaction and the diversity of the core region was analyzed by the single strand conformation polymorphism analysis. Using this method, single or multiple DNA bands were observed in each patient, and representative bands showed different nucleotide sequences. Comparison of single strand conformation polymorphism patterns revealed that the population of quasispecies changed during the course of chronic infection. These changes were more remarkable in patients with high serum alanine aminotransferase levels than those with low serum alanine aminotransferase levels. Thus, sequential variations exist in the core region of hepatitis C virus in same individuals, and the population of quasispecies as determined by the sequence of the core region changes during the course of infection, which might be related to cytopathic effects of hepatitis C virus.