The Impact of Hepatitis C Virus Entry on Viral Tropism

Abstract

Uptake of hepatitis C virus (HCV) into hepatocytes is an orchestrated process, involving numerous host factors, virion-associated lipoproteins and a growing number of cell-associated factors. Several of these factors likely contribute to the hepatotropism and limited host range of this virus. Discerning the minimal set of human-specific factors required for viral uptake into non-human cells has facilitated the development of small animal models with inheritable HCV susceptibility. This review summarizes current knowledge of host factors required for HCV entry, the molecular mechanisms underlying HCV entry into hepatocytes, and aspects of viral entry contributing to HCV host tropism.

Altered Glycosylation Patterns Increase Immunogenicity of a Subunit Hepatitis C Virus Vaccine, Inducing Neutralizing Antibodies Which Confer Protection in Mice

“…We should point out that this mouse model is not without caveats. For example, since not all of the identified human receptors/cofactors for HCV (17) are present in the model, it may be easier to prevent infection in the model than with natural infection. Nevertheless, we have previously shown that levels of protection correlate well with the immunogenicity of vectored vaccines in the model (12), and thus, such humanized mice seem adequate for evaluating the efficacy of our recombinant HCV vaccine.…”

“…However, due to the extreme genetic and antigenic diversity across and within HCV genotypes, this has been a particularly challenging goal (15). The HCV envelope proteins E1 and E2 are responsible for mediating HCV entry into target cells by direct or indirect interaction with numerous host molecules (16,17) and are thus the natural targets of NAbs (18). Consequently, all experimental HCV vaccines that aim to generate NAbs contain E2 and/or E1 components in a variety of modalities or prime-boost regimens (19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”

The Molecular Biology of Pestiviruses

“…Nevertheless, experiments with CSFV and antibodies against the porcine CD46 suggest that porcine CD46 plays a role for CSFV entry, but the inhibitory effect remained rather weak, suggesting involvement of additional factors (Dräger, Beer, & Blome, 2015). The related HCV was shown to use at least four different entry factors (for a review, see Ding, von Schaewen, & Ploss, 2014;. For pestiviruses, evidence so far suggests that a first attachment might be due to the interaction of E rns with glycosaminoglycans (Hulst et al, 2000Iqbal et al, 2000).…”

Roles of Lipoproteins and Apolipoproteins in Particle Formation of Hepatitis C Virus

“…Among the many host factors, human-specific CD81 and OCLN are sufficient for entry and replication of HCV in murine cells in vitro and in vivo, suggesting that the host tropism of HCV is mostly defined by entry receptors [81]. Interestingly, mouse hepatic cell lines endogenously expressing miR-122 and ApoE support the replication of viral RNA and formation of infectious HCV particles, indicating that apolipoproteins are not involved in the host tropism of HCV [82,83].…”