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. 2006;3(2):29-34.
doi: 10.7150/ijms.3.29. Epub 2006 Apr 1.

Molecular virology of hepatitis C virus (HCV): 2006 update

Volker Brass  1 , Darius Moradpour, Hubert E Blum
Affiliations

Molecular virology of hepatitis C virus (HCV): 2006 update

Volker Brass et al. Int J Med Sci. 2006.

Abstract

Fascinating progress in the understanding of the molecular biology of hepatitis C virus (HCV) was achieved recently. The replicon system revolutionized the investigation of HCV RNA replication and facilitated drug discovery. Novel systems for functional analyses of the HCV glycoproteins allowed the validation of HCV receptor candidates and the investigation of cell entry mechanisms. Most recently, recombinant infectious HCV could be produced in cell culture, rendering all steps of the viral life cycle, including entry and release of viral particles, amenable to systematic analysis. In this review, we summarize recent advances and discuss future research directions.

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Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1
Life cycle of HCV. The steps of the viral life cycle are depicted schematically. The topology of HCV structural and nonstructural proteins at the endoplasmic reticulum (ER) membrane is shown. HCV RNA replication occurs in a specific membrane alteration, the membranous web (MW). IRES-mediated translation and polyprotein processing as well as membranous web formation and RNA replication, illustrated here as separate steps for simplicity, may occur in a tightly coupled manner
Figure 2
Figure 2
Comparison of different replicon systems. A selection of different bicistronic and monocistronic replicon constructs including subgenomic and full-length HCV sequences is depicted schematically. Stably replicating systems are equipped among others with a neomycin phosphotransferase or a hygromycin phosphotransferase cassette that allow selection of cells with continuous RNA replication. Transient systems include a marker gene that allows quantification 48 h after transient transfection. In general, luciferase (Luc) is used as easily quantifiable enzyme in this context and values are normalized based on the amount of input RNA. Monocistronic replicon constructs avoid the translation of proteins from the heterologous encephalomyocarditis virus (EMCV) IRES. The resistance gene is released after cleavage via a ubiquitin sequence (Ubi)
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