Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles

Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles

Apolipoprotein B (ApoB) and ApoE have been shown to participate in the particle formation and the tissue tropism of hepatitis C virus (HCV), but their precise roles remain uncertain. Here we show that amphipathic α-helices in the apolipoproteins participate in the HCV particle formation by using zin...

Full description

Bibliographic Details
Main Authors: Fukuhara, Takasuke, Wada, Masami, Nakamura, Shota, Ono, Chikako, Shiokawa, Mai, Yamamoto, Satomi, Motomura, Takashi, Okamoto, Toru, Okuzaki, Daisuke, Yamamoto, Masahiro, Saito, Izumu, Wakita, Takaji, Koike, Kazuhiko, Matsuura, Yoshiharu
Format: Online
Language:English
Published: Public Library of Science 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263759/
id pubmed-4263759
recordtype oai_dc
spelling pubmed-42637592014-12-19 Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles Fukuhara, Takasuke Wada, Masami Nakamura, Shota Ono, Chikako Shiokawa, Mai Yamamoto, Satomi Motomura, Takashi Okamoto, Toru Okuzaki, Daisuke Yamamoto, Masahiro Saito, Izumu Wakita, Takaji Koike, Kazuhiko Matsuura, Yoshiharu Research Article Apolipoprotein B (ApoB) and ApoE have been shown to participate in the particle formation and the tissue tropism of hepatitis C virus (HCV), but their precise roles remain uncertain. Here we show that amphipathic α-helices in the apolipoproteins participate in the HCV particle formation by using zinc finger nucleases-mediated apolipoprotein B (ApoB) and/or ApoE gene knockout Huh7 cells. Although Huh7 cells deficient in either ApoB or ApoE gene exhibited slight reduction of particles formation, knockout of both ApoB and ApoE genes in Huh7 (DKO) cells severely impaired the formation of infectious HCV particles, suggesting that ApoB and ApoE have redundant roles in the formation of infectious HCV particles. cDNA microarray analyses revealed that ApoB and ApoE are dominantly expressed in Huh7 cells, in contrast to the high level expression of all of the exchangeable apolipoproteins, including ApoA1, ApoA2, ApoC1, ApoC2 and ApoC3 in human liver tissues. The exogenous expression of not only ApoE, but also other exchangeable apolipoproteins rescued the infectious particle formation of HCV in DKO cells. In addition, expression of these apolipoproteins facilitated the formation of infectious particles of genotype 1b and 3a chimeric viruses. Furthermore, expression of amphipathic α-helices in the exchangeable apolipoproteins facilitated the particle formation in DKO cells through an interaction with viral particles. These results suggest that amphipathic α-helices in the exchangeable apolipoproteins play crucial roles in the infectious particle formation of HCV and provide clues to the understanding of life cycle of HCV and the development of novel anti-HCV therapeutics targeting for viral assembly. Public Library of Science 2014-12-11 /pmc/articles/PMC4263759/ /pubmed/25502789 http://dx.doi.org/10.1371/journal.ppat.1004534 Text en © 2014 Fukuhara et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Fukuhara, Takasuke
Wada, Masami
Nakamura, Shota
Ono, Chikako
Shiokawa, Mai
Yamamoto, Satomi
Motomura, Takashi
Okamoto, Toru
Okuzaki, Daisuke
Yamamoto, Masahiro
Saito, Izumu
Wakita, Takaji
Koike, Kazuhiko
Matsuura, Yoshiharu
spellingShingle Fukuhara, Takasuke
Wada, Masami
Nakamura, Shota
Ono, Chikako
Shiokawa, Mai
Yamamoto, Satomi
Motomura, Takashi
Okamoto, Toru
Okuzaki, Daisuke
Yamamoto, Masahiro
Saito, Izumu
Wakita, Takaji
Koike, Kazuhiko
Matsuura, Yoshiharu
Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles
author_facet Fukuhara, Takasuke
Wada, Masami
Nakamura, Shota
Ono, Chikako
Shiokawa, Mai
Yamamoto, Satomi
Motomura, Takashi
Okamoto, Toru
Okuzaki, Daisuke
Yamamoto, Masahiro
Saito, Izumu
Wakita, Takaji
Koike, Kazuhiko
Matsuura, Yoshiharu
author_sort Fukuhara, Takasuke
title Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles
title_short Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles
title_full Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles
title_fullStr Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles
title_full_unstemmed Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles
title_sort amphipathic α-helices in apolipoproteins are crucial to the formation of infectious hepatitis c virus particles
description Apolipoprotein B (ApoB) and ApoE have been shown to participate in the particle formation and the tissue tropism of hepatitis C virus (HCV), but their precise roles remain uncertain. Here we show that amphipathic α-helices in the apolipoproteins participate in the HCV particle formation by using zinc finger nucleases-mediated apolipoprotein B (ApoB) and/or ApoE gene knockout Huh7 cells. Although Huh7 cells deficient in either ApoB or ApoE gene exhibited slight reduction of particles formation, knockout of both ApoB and ApoE genes in Huh7 (DKO) cells severely impaired the formation of infectious HCV particles, suggesting that ApoB and ApoE have redundant roles in the formation of infectious HCV particles. cDNA microarray analyses revealed that ApoB and ApoE are dominantly expressed in Huh7 cells, in contrast to the high level expression of all of the exchangeable apolipoproteins, including ApoA1, ApoA2, ApoC1, ApoC2 and ApoC3 in human liver tissues. The exogenous expression of not only ApoE, but also other exchangeable apolipoproteins rescued the infectious particle formation of HCV in DKO cells. In addition, expression of these apolipoproteins facilitated the formation of infectious particles of genotype 1b and 3a chimeric viruses. Furthermore, expression of amphipathic α-helices in the exchangeable apolipoproteins facilitated the particle formation in DKO cells through an interaction with viral particles. These results suggest that amphipathic α-helices in the exchangeable apolipoproteins play crucial roles in the infectious particle formation of HCV and provide clues to the understanding of life cycle of HCV and the development of novel anti-HCV therapeutics targeting for viral assembly.
publisher Public Library of Science
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263759/
_version_ 1613166701716701184

Similar Items