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HCV assembly : from clustering of viral assembly factors to envelopment and lipidation of particles

Abstract : Hepatitis C virus (HCV) is detected in the sera of infected patients as lipidated infectious particles of very-low density. HCV is an enveloped virus whose assembly of viral particles occurs at the endoplasmic reticulum membrane following sequential cleavage of its polyprotein and its maturation as structural and non-structural viral proteins. In this work, we aimed at better understanding the mechanisms of assembly, envelopment and secretion of infectious particles. In a first study, we highlighted the functional connection between replication complexes and assembly sites. In a second study, we showed that p7 dose-dependently slows down the ER-to-Golgi traffic, leading to intracellular retention of E2 viral glycoprotein. In addition, we showed that cleavage of an E2p7 precursor protein controls E2 intracellular expression and secretion levels of subviral particles and infectious virions. Finally, we also highlighted that p7 N-terminal extremity governs the specific infectivity of the infectious particles by coordinating the encountering of the nucleocapsid components with the glycoproteins and the envelopment of the nucleocapsids. In a third study, we discovered specific functions and factors from serum, producer cells, and HCV sequences that modulate lipidation of viral particles during their assembly and secretion. Altogether, these different works contributed at better understanding the steps of HCV assembly and the mechanisms modulating i) the transfer of viral RNAs from replication complexes to assembly sites, ii) the encountering of the nucleocapsids and glycoproteins followed by virion envelopment, and finally, iii) the acquisition of lipids by viral particles
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Submitted on : Friday, November 2, 2018 - 12:14:07 PM
Last modification on : Wednesday, November 20, 2019 - 3:01:44 AM
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  • HAL Id : tel-01911091, version 1


Solène Denolly. HCV assembly : from clustering of viral assembly factors to envelopment and lipidation of particles. Virology. Université de Lyon, 2018. English. ⟨NNT : 2018LYSE1085⟩. ⟨tel-01911091⟩



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