Hepatitis C virus population dynamics in human lymphocytes and hepatocytes infected in vitro.

Abstract

We previously found two cell lines (MT-2 and PH5CH) that were susceptible to hepatitis C virus (HCV) infection. Analysis of the infectivity of sera from HCV-positive blood donors for MT-2 and PH5CH cells suggested the cell tropism of HCV. To investigate further the cell tropism of HCV, the dynamics of HCV populations during culture were examined using three MT-2 clones and three PH5CH clones, infected with inoculum 1B-2. To type HCV populations in these infected cells, the HCV hypervariable region 1 (HVR1) in these cloned cells was characterized by sequence analysis and HpaII digestion analysis, which could distinguish three major HVR1 types (I, II and III) derived from the inoculum 1B-2. It was found that genomes containing HVR1 type I became predominant in MT-2 clones, and genomes containing HVR1 type II became predominant in PH5CH clones during culture after inoculation. These results suggest that inoculum 1B-2 contains both lymphotropic and hepatotropic HCV species, which can be distinguished by HVR1 type. To search for cell type-specific sequences in regions other than HVR1, three HCV cDNA clones (3.4 kb of the 5' noncoding region to the nonstructural 2 region) containing HVR1 type I obtained from HCV-infected MT-2C cells, and three HCV cDNA clones containing HVR1 type II obtained from HCV-infected PH5CH7 cells were sequenced. Following a comparison of the sequences, 11 amino acids were identified as candidates for determinants of the cell tropism of HCV.