Role of macrophages and monocytes in hepatitis C virus infections

Abstract

A number of studies conducted over many years have shown that hepatitis C virus (HCV) can infect a variety of cell types. In vivo infection of monocytes, macrophages, and dendritic cells by HCV has been frequently shown by a number of researchers. These studies have demonstrated replication of HCV by detecting the presence of both negative genomic strands and a variety of non-structural HCV proteins in infected cells. In addition, analyses of genome sequences have also shown that different cell types can harbor different HCV variants. Investigators have also done preliminary studies of which cellular genes are affected by HCV infection, but there have not yet been a sufficient number of these studies to understand the effects of infection on these cells. Analyses of in vitro HCV replication have shown that monocytes, macrophages and dendritic cells can be infected by HCV from patient sera or plasma. These studies suggest that entry and cellular locations may vary between different cell types. Some studies suggest that macrophages may preferentially allow HCV genotype 1 to replicate, but macrophages do not appear to select particular hypervariable regions. Overall, these studies agree with a model where monocytes and macrophages act as an amplification system, in which these cells are infected and show few cytopathic effects, but continuously produce HCV. This allows them to produce virus over an extended time and allows its spread to other cell types.

Keywords: Dendritic cells; Hepatitis C virus; Hepatitis C virus replication; Macrophages; Monocytes.

Figure 1

Isolation method for studying in vitro replication of hepatitis C virus. Macrophages are generated from mononuclear cells in fetal cord blood and infected by hepatitis C virus (HCV). Adapted from reference[55]. EBV: Epstein-Barr virus; PWM: Pokeweed mitogen; PMA: Phorbol-12-myristate-13-acetate; PBMC: Peripheral blood mononuclear cells.