Abstract
Two to three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Here, we have identified a partner of CD81, EWI-2wint, which is expressed in several cell lines but not in hepatocytes. Ectopic expression of EWI-2wint in a hepatoma cell line susceptible to HCV infection blocked viral entry by inhibiting the interaction between the HCV envelope glycoproteins and CD81. This finding suggests that, in addition to the presence of specific entry factors in the hepatocytes, the lack of a specific inhibitor can contribute to the hepatotropism of HCV. This is the first example of a pathogen gaining entry into host cells that lack a specific inhibitory factor.
Highlights
Hepatitis C virus (HCV) infection is a global public health problem affecting over 130 million individuals worldwide; its symptoms including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma [1]
We analysed the interaction between E1E2 heterodimers and CD81 in several cell lines lysed in different detergent conditions (Figure 1A and Table 1)
Our results suggest that a CD81 partner, present on Daudi and Ramos cells, blocks the interaction between CD81 and HCV glycoproteins
Summary
Hepatitis C virus (HCV) infection is a global public health problem affecting over 130 million individuals worldwide; its symptoms including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma [1]. Due to the lack of a cell culture system supporting production of infectious virus particles, several surrogate models have been developed to facilitate analysis of the HCV life cycle. Among these models, pseudoparticles (HCVpp), consisting of native HCV envelope glycoproteins assembled onto retroviral core particles [3,4] have been useful in investigating the HCV entry process. Production of infectious HCV particles in cell culture (HCVcc) has become possible [5,6,7]. This powerful system is based on the transfection of the human hepatoma cell line Huh-7 with the cloned JFH1 genome that replicates and produces infectious particles
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