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Host-derived apolipoproteins play comparable roles with viral secretory proteins E(rns) and NS1 in the infectious particle formation of Flaviviridae

Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV) particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein E(rns) or...

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Autores principales: Fukuhara, Takasuke, Tamura, Tomokazu, Ono, Chikako, Shiokawa, Mai, Mori, Hiroyuki, Uemura, Kentaro, Yamamoto, Satomi, Kurihara, Takeshi, Okamoto, Toru, Suzuki, Ryosuke, Yoshii, Kentaro, Kurosu, Takeshi, Igarashi, Manabu, Aoki, Hiroshi, Sakoda, Yoshihiro, Matsuura, Yoshiharu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500379/
https://www.ncbi.nlm.nih.gov/pubmed/28644867
http://dx.doi.org/10.1371/journal.ppat.1006475
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author Fukuhara, Takasuke
Tamura, Tomokazu
Ono, Chikako
Shiokawa, Mai
Mori, Hiroyuki
Uemura, Kentaro
Yamamoto, Satomi
Kurihara, Takeshi
Okamoto, Toru
Suzuki, Ryosuke
Yoshii, Kentaro
Kurosu, Takeshi
Igarashi, Manabu
Aoki, Hiroshi
Sakoda, Yoshihiro
Matsuura, Yoshiharu
author_facet Fukuhara, Takasuke
Tamura, Tomokazu
Ono, Chikako
Shiokawa, Mai
Mori, Hiroyuki
Uemura, Kentaro
Yamamoto, Satomi
Kurihara, Takeshi
Okamoto, Toru
Suzuki, Ryosuke
Yoshii, Kentaro
Kurosu, Takeshi
Igarashi, Manabu
Aoki, Hiroshi
Sakoda, Yoshihiro
Matsuura, Yoshiharu
author_sort Fukuhara, Takasuke
collection PubMed
description Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV) particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein E(rns) or a non-structural protein 1 (NS1) as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of E(rns) are important for anchoring to viral membrane. Here we show that host-derived apolipoproteins play functional roles similar to those of virally encoded E(rns) and NS1 in the formation of infectious particles. We examined whether E(rns) and NS1 could compensate for the role of apolipoproteins in particle formation of HCV in apolipoprotein B (ApoB) and ApoE double-knockout Huh7 (BE-KO), and non-hepatic 293T cells. We found that exogenous expression of either E(rns) or NS1 rescued infectious particle formation of HCV in the BE-KO and 293T cells. In addition, expression of apolipoproteins or NS1 partially rescued the production of infectious pestivirus particles in cells upon electroporation with an E(rns)-deleted non-infectious RNA. As with exchangeable apolipoproteins, the C-terminal amphipathic α-helices of E(rns) play the functional roles in the formation of infectious HCV or pestivirus particles. These results strongly suggest that the host- and virus-derived secretory glycoproteins have overlapping roles in the viral life cycle of Flaviviridae, especially in the maturation of infectious particles, while E(rns) and NS1 also participate in replication complex formation and viral entry, respectively. Considering the abundant hepatic expression and liver-specific propagation of these apolipoproteins, HCV might have evolved to utilize them in the formation of infectious particles through deletion of a secretory viral glycoprotein gene.
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spelling pubmed-55003792017-07-11 Host-derived apolipoproteins play comparable roles with viral secretory proteins E(rns) and NS1 in the infectious particle formation of Flaviviridae Fukuhara, Takasuke Tamura, Tomokazu Ono, Chikako Shiokawa, Mai Mori, Hiroyuki Uemura, Kentaro Yamamoto, Satomi Kurihara, Takeshi Okamoto, Toru Suzuki, Ryosuke Yoshii, Kentaro Kurosu, Takeshi Igarashi, Manabu Aoki, Hiroshi Sakoda, Yoshihiro Matsuura, Yoshiharu PLoS Pathog Research Article Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV) particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein E(rns) or a non-structural protein 1 (NS1) as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of E(rns) are important for anchoring to viral membrane. Here we show that host-derived apolipoproteins play functional roles similar to those of virally encoded E(rns) and NS1 in the formation of infectious particles. We examined whether E(rns) and NS1 could compensate for the role of apolipoproteins in particle formation of HCV in apolipoprotein B (ApoB) and ApoE double-knockout Huh7 (BE-KO), and non-hepatic 293T cells. We found that exogenous expression of either E(rns) or NS1 rescued infectious particle formation of HCV in the BE-KO and 293T cells. In addition, expression of apolipoproteins or NS1 partially rescued the production of infectious pestivirus particles in cells upon electroporation with an E(rns)-deleted non-infectious RNA. As with exchangeable apolipoproteins, the C-terminal amphipathic α-helices of E(rns) play the functional roles in the formation of infectious HCV or pestivirus particles. These results strongly suggest that the host- and virus-derived secretory glycoproteins have overlapping roles in the viral life cycle of Flaviviridae, especially in the maturation of infectious particles, while E(rns) and NS1 also participate in replication complex formation and viral entry, respectively. Considering the abundant hepatic expression and liver-specific propagation of these apolipoproteins, HCV might have evolved to utilize them in the formation of infectious particles through deletion of a secretory viral glycoprotein gene. Public Library of Science 2017-06-23 /pmc/articles/PMC5500379/ /pubmed/28644867 http://dx.doi.org/10.1371/journal.ppat.1006475 Text en © 2017 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Fukuhara, Takasuke
Tamura, Tomokazu
Ono, Chikako
Shiokawa, Mai
Mori, Hiroyuki
Uemura, Kentaro
Yamamoto, Satomi
Kurihara, Takeshi
Okamoto, Toru
Suzuki, Ryosuke
Yoshii, Kentaro
Kurosu, Takeshi
Igarashi, Manabu
Aoki, Hiroshi
Sakoda, Yoshihiro
Matsuura, Yoshiharu
Host-derived apolipoproteins play comparable roles with viral secretory proteins E(rns) and NS1 in the infectious particle formation of Flaviviridae
title Host-derived apolipoproteins play comparable roles with viral secretory proteins E(rns) and NS1 in the infectious particle formation of Flaviviridae
title_full Host-derived apolipoproteins play comparable roles with viral secretory proteins E(rns) and NS1 in the infectious particle formation of Flaviviridae
title_fullStr Host-derived apolipoproteins play comparable roles with viral secretory proteins E(rns) and NS1 in the infectious particle formation of Flaviviridae
title_full_unstemmed Host-derived apolipoproteins play comparable roles with viral secretory proteins E(rns) and NS1 in the infectious particle formation of Flaviviridae
title_short Host-derived apolipoproteins play comparable roles with viral secretory proteins E(rns) and NS1 in the infectious particle formation of Flaviviridae
title_sort host-derived apolipoproteins play comparable roles with viral secretory proteins e(rns) and ns1 in the infectious particle formation of flaviviridae
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500379/
https://www.ncbi.nlm.nih.gov/pubmed/28644867
http://dx.doi.org/10.1371/journal.ppat.1006475
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