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Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles
In vitro systems have been developed for the study of hepatitis C virus (HCV) infection and have revealed many details of the life cycle of HCV. Apolipoprotein B (ApoB) and ApoE have been shown to play crucial roles in the particle formation of HCV, based on data obtained by siRNA-mediated gene knockdown and overexpression of the proteins. However, precise roles of the apolipoproteins in HCV assembly have not been elucidated yet. In this study, we show that infectious particle formation of HCV in Huh7 cells was severely impaired by the knockout of both ApoB and ApoE genes by artificial nucleases, and this reduction was cancelled by the expression of not only ApoE, but also other exchangeable apolipoproteins, including ApoA1, ApoA2, ApoC1, ApoC2 and ApoC3. In addition, expression of amphipathic α-helices in the exchangeable apolipoproteins restored the infectious particle formation in the double-knockout cells through an interaction with viral particles. These results provide clues to the understanding of life cycle of HCV and the development of novel antivirals to HCV.
Vyšlo v časopise: Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004534
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004534Souhrn
In vitro systems have been developed for the study of hepatitis C virus (HCV) infection and have revealed many details of the life cycle of HCV. Apolipoprotein B (ApoB) and ApoE have been shown to play crucial roles in the particle formation of HCV, based on data obtained by siRNA-mediated gene knockdown and overexpression of the proteins. However, precise roles of the apolipoproteins in HCV assembly have not been elucidated yet. In this study, we show that infectious particle formation of HCV in Huh7 cells was severely impaired by the knockout of both ApoB and ApoE genes by artificial nucleases, and this reduction was cancelled by the expression of not only ApoE, but also other exchangeable apolipoproteins, including ApoA1, ApoA2, ApoC1, ApoC2 and ApoC3. In addition, expression of amphipathic α-helices in the exchangeable apolipoproteins restored the infectious particle formation in the double-knockout cells through an interaction with viral particles. These results provide clues to the understanding of life cycle of HCV and the development of novel antivirals to HCV.
Zdroje
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