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• W2061517295 endingPage "e1002466" @default.
• W2061517295 startingPage "e1002466" @default.
• W2061517295 abstract "The current model of hepatitis C virus (HCV) production involves the assembly of virions on or near the surface of lipid droplets, envelopment at the ER in association with components of VLDL synthesis, and egress via the secretory pathway. However, the cellular requirements for and a mechanistic understanding of HCV secretion are incomplete at best. We combined an RNA interference (RNAi) analysis of host factors for infectious HCV secretion with the development of live cell imaging of HCV core trafficking to gain a detailed understanding of HCV egress. RNAi studies identified multiple components of the secretory pathway, including ER to Golgi trafficking, lipid and protein kinases that regulate budding from the trans-Golgi network (TGN), VAMP1 vesicles and adaptor proteins, and the recycling endosome. Our results support a model wherein HCV is infectious upon envelopment at the ER and exits the cell via the secretory pathway. We next constructed infectious HCV with a tetracysteine (TC) tag insertion in core (TC-core) to monitor the dynamics of HCV core trafficking in association with its cellular cofactors. In order to isolate core protein movements associated with infectious HCV secretion, only trafficking events that required the essential HCV assembly factor NS2 were quantified. TC-core traffics to the cell periphery along microtubules and this movement can be inhibited by nocodazole. Sub-populations of TC-core localize to the Golgi and co-traffic with components of the recycling endosome. Silencing of the recycling endosome component Rab11a results in the accumulation of HCV core at the Golgi. The majority of dynamic core traffics in association with apolipoprotein E (ApoE) and VAMP1 vesicles. This study identifies many new host cofactors of HCV egress, while presenting dynamic studies of HCV core trafficking in infected cells." @default.
• W2061517295 created "2016-06-24" @default.
• W2061517295 creator A5018467762 @default.
• W2061517295 creator A5050923432 @default.
• W2061517295 creator A5064828779 @default.
• W2061517295 creator A5068215400 @default.
• W2061517295 creator A5073168358 @default.
• W2061517295 creator A5074899537 @default.
• W2061517295 date "2012-01-05" @default.
• W2061517295 modified "2023-10-15" @default.
• W2061517295 title "Molecular Determinants and Dynamics of Hepatitis C Virus Secretion" @default.
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