Genetic diversity and tissue compartmentalization of the hepatitis C virus genome in blood mononuclear cells, liver, and serum from chronic hepatitis C patients

Abstract

The degree of genetic variability in the hypervariable region 1 of hepatitis C virus (HCV) was analyzed by cloning and sequencing HCV genomes obtained in paired samples of serum, liver tissue, and peripheral blood mononuclear cells (PBMC) from four chronic hepatitis C patients. Genetic variability in serum was higher than in liver tissue or PBMC at the level of complexity (the number of different sequences obtained from each type of tissue) as well as at the level of genetic distance between all pairs of sequences within each tissue (compared by the Student t test; P < 0.001 for two patients and P < 0.01 for another). The spectrum of viral genomes differed among the three types of tissue, as shown by segregation of sequences according to their tissue of origin in phylogenetic analysis and by statistical analysis of mean genetic distances observed between sequences obtained from different tissues (P < 0.001), but sequences from liver tissue and PBMC were more closely related to each other than to those from serum.

FIG. 1

Distribution of genetic distances between all possible pairs of sequences within each type of tissue studied (PBMC, liver tissue, and serum) on nucleotide (A) and amino acid (B) levels. Genetic distances (in increments of 0.05) are recorded on the x axes, while the percentages of times scored are recorded on the y axes.

FIG. 2

Unrooted phylogenetic trees constructed by the neighbor-joining method from the analysis of the HVR1 sequences obtained from paired samples of PBMC, liver tissue, and serum of patient 4, on nucleotide (left) and amino acid (right) levels.