Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.2777
Revised: November 27, 2013
Accepted: January 6, 2014
Published online: March 21, 2014
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.
Core tip: We review the evidence of infection of monocytes and macrophages by hepatitis C virus (HCV), both in vivo and in vitro. There are two innovative ideas: (1) the hypervariable region of HCV may vary due to host range of variants in addition to immune pressure; and (2) a novel model of the role of macrophages and monocytes in HCV infections is proposed that is consistent with current evidence.