Principles of HCV assembly and entry and their role in virus persistence
About this project
Fifty to 90 percent of all HCV infections are chronic. The association of the virus with lipoproteins contributes to its persistence by directly influencing virus entry into the liver cell and protecting it from neutralizing antibodies.
We are investigating host factors and viral factors that influence the association of the virus with lipoproteins to elucidate their role in viral persistence. The interaction of HCV with lipoproteins begins during virus assembly. This occurs in the so-called “lipid droplets”, cellular organelles that store lipids (Figure 1: Vieyres et al. PLoS Pathogens 2016). HCV uses cellular lipases such as ATGL to mobilize lipids for the formation of HCV lipoviroparticles (Vieyres et al. PLoS Pathogens 2020).
Following the release of HCV particles, circulating lipoproteins are incorporated into these particles (Bankwitz et al. J Hepatol 2017). This maturation process promotes viral attachment to liver cells and antibody protection (Figure 2 and Bankwitz et al. J Hepatol 2017). Supported by SFB900, we investigate the cellular and viral proteins that mediate the interaction between HCV and lipoproteins. Ultimately, the insights gained into how HCV escapes the antibody response with the help of lipoproteins will guide the development of a vaccine against HCV.
