Abstract
The mechanisms by which HCV escapes the host immune response and gains entry into target cells are still largely unknown, although new methods in molecular virology are greatly contributing to the advancement of knowledge in this field. Model systems for the study of HCV cell entry include HCV-like particles, HCV pseudoparticles, cell-culture-produced HCV, and the tupaia animal model. Following the identification of tetraspanin CD81 with the use of recombinant E2 glycoprotein, additional cell-surface molecules have been shown to play a role as viral receptors on host cells, namely scavenger receptor (SR) BI, tight-junction proteins such as claudin-1 and occludin, glycosaminoglycans, and two membrane proteins of the C-type lectin family. It is possible that different circulating forms of HCV activate different pathways of cell entry. Nevertheless, lipoproteins and, in particular, LDL receptors are essential in virus cell entry. In the initial step, ApoB-associated HCV is bound and internalized through the interplay of virus-associated VLDL and SR-BI, which possibly implies the involvement of LDL receptors and glycosaminoglycans. In the next step, HCV binds to the SR-BI/CD81 complex and is transferred to the tight-junction proteins. Following clathrin-mediated endocytosis, the virus initiates fusion and releases its RNA genome into the cytosol. Further clarification of the biomolecular mechanisms underlying cellular entry of HCV will hopefully result in the identification of novel therapeutic compounds that selectively target entry.
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© 2012 Springer-Verlag Italia
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Dammacco, F., Racanelli, V. (2012). Mechanisms of Cell Entry of Hepatitis C Virus. In: Dammacco, F. (eds) HCV Infection and Cryoglobulinemia. Springer, Milano. https://doi.org/10.1007/978-88-470-1705-4_7
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DOI: https://doi.org/10.1007/978-88-470-1705-4_7
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