COMPARISON OF THE HYPERVARIABLE REGION OF HEPATITIS-C VIRUS GENOMES IN PLASMA AND LIVER

Nucleotide sequences of the hypervariable region of hepatitis C virus genomes obtained from plasma change rapidly during the course of infec tion and are believed to play a part in immunological escape and conse quently in the development of persistent infection. It is not known, h owever, whether these changes also occur in the liver. To clarify this aspect, RNA was extracted from the plasma and liver tissue of eight p atients with chronic hepatitis C. After cDNA synthesis, DNA fragments that included the hypervariable region were amplified by the polymeras e chain reaction. Consensus nucleotide sequences were determined direc tly from the polymerase chain reaction products by the dideoxy chain t ermination method, The diversity of the hypervariable region was analy zed further by the polymerase chain reaction-single strand conformatio n polymorphism analysis. Consensus nucleotide sequences of the hyperva riable region were identical between the plasma and the liver in each patient. The polymerase chain reaction-single strand conformation poly morphism analysis showed multiple DNA bands that represented different hypervariable region sequences. Comparison of the single strand confo rmation polymorphism patterns revealed that the number, the mobility, and the density of bands were the same between the plasma and the live r. It is concluded that the population and the diversity of hepatitis C virus quasispecies as detected by the hypervariable region sequence are the same between the plasma and the liver despite rapid mutations, indicating that rapid changes in the population of hepatitis C virus quasispecies also occur in the liver. (C) 1995 Wiley-Liss, Inc.