Full-length GB virus C (hepatitis G virus) RNA transcripts are infectious in primary CD4-positive T cells

GB virus C (GBV-C or hepatitis G virus) is a recently described flavivirus which frequently leads to chronic viremia in humans. Although GBV-C is asso ciated with acute posttransfusion hepatitis, it is not clear if the virus i s pathogenic for humans. We constructed a full-length cDNA from the plasma of a person with chronic GBV-C viremia. Peripheral blood mononuclear cells (PBMCs) transfected with full-length RNA transcripts from this GBV-C clone resulted in viral replication. This was demonstrated by serial passage of v irus from cell culture supernatants, detection of increasing concentrations of positive- and negative-sense GBV-C RNA over time, and the detection of the GBV-C E2 antigen by confocal microscopy. In addition, two types of GBV- C particles were identified in cell lysates; these particles had buoyant de nsities of 1.06 and 1.12 to 1.17 g/ml in sucrose gradients. PBMCs sorted fo r expression of CD4 contained 100-fold-more GBV-C RNA than CD4-negative cel ls. Taken together, these data demonstrate that RNA transcripts from GBV-C full-length cDNA are infectious in primary CD4-positive T cells. In contras t, RNA transcripts from an infectious hepatitis C virus clone did not repli cate in the same cell culture system. Infectious RNA transcripts from GBV-C cDNA should prove useful for studying viral replication and may allow iden tification of differences between GBV-C and hepatitis C virus cultivation i n vitro.