Infection and propagation of hepatitis C virus in human CD4⁺ and CD8⁺ T lymphocytes in vitro

Abstract

Accumulated molecular and clinical evidence indicate that human immune cells can support replication of hepatitis C virus (HCV). The aim of this study was to investigate the ability of authentic, plasma-occurring HCV to infect human CD4⁺ and CD8⁺ T lymphocytes in vitro. For this purpose, we adopted the previously established in vitro HCV replication system in total T cells derived from cultured normal human PBMC by employing affinity-purified CD4⁺ and CD8⁺ T lymphocytes as targets. Using this system, we were able to demonstrate that molecularly intact HCV can infect and productively replicate in both CD4⁺ and CD8⁺ T lymphocytes, albeit at low levels, by documenting: (1) Presence of HCV positive and replicative (negative) strands in infected cells; (2) Intracytoplasmic localization of viral proteins; (3) Emergence of new HCV variants in the de novo infected cells, and (4) Release of HCV RNA-reactive particles from the infected cells with biophysical properties distinct from those of virions in inocula used to infect these cells.