Nonrandom distribution of hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cell subsets

The existence of an extrahepatic reservoir of hepatitis C virus (HCV) is su ggested by differences in quasispecies composition between the liver, perip heral blood mononuclear cells, and serum. We studied HCV RNA compartmentali zation in the plasma of nine patients, in CD19(+), CD8(+), and CD4(+) posit ively selected cells, and also in the negatively selected cell fraction (NF ). HCV RNA was detected in all plasma samples, in seven of nine CD19(+), th ree of eight CD8+, and one of nine CD4(+) cell samples, and in seven of eig ht NF cells. Cloning and sequencing of HVR1 in two patients showed a sequen ce grouping: quasispecies from a given compartment (all studied compartment s for one patient and CD8(+) and NF for the other) were statistically more genetically like each other than like quasispecies from any other compartme nt. The characteristics of amino acid and nucleotide substitutions suggeste d the same structural constraints on HVR1, even in very divergent strains f rom the cellular compartments, and homogeneous selection pressure on the di fferent compartments. These findings demonstrate the compartmental distribu tion of HCV quasispecies within peripheral blood cell subsets and have impo rtant implications for the study of extrahepatic HCV replication and intera ction with the immune system.