Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.

Hepatitis C virus (HCV) infection induces the degradation and decreases the secretion of apolipoprotein B (ApoB). Impaired production and secretion of ApoB-containing lipoprotein is associated with an increase in hepatic steatosis. Therefore, HCV infection-induced degradation of ApoB may contribute...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Bei Wang, Yue Zhu, Congci Yu, Chongyang Zhang, Qing Tang, He Huang, Zhendong Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/63f99eb007dd407484c4dbb557f0498d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:63f99eb007dd407484c4dbb557f0498d
record_format	dspace
spelling	oai:doaj.org-article:63f99eb007dd407484c4dbb557f0498d2021-12-02T20:00:13ZHepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.1553-73661553-737410.1371/journal.ppat.1009889https://doaj.org/article/63f99eb007dd407484c4dbb557f0498d2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009889https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Hepatitis C virus (HCV) infection induces the degradation and decreases the secretion of apolipoprotein B (ApoB). Impaired production and secretion of ApoB-containing lipoprotein is associated with an increase in hepatic steatosis. Therefore, HCV infection-induced degradation of ApoB may contribute to hepatic steatosis and decreased lipoprotein secretion, but the mechanism of HCV infection-induced ApoB degradation has not been completely elucidated. In this study, we found that the ApoB level in HCV-infected cells was regulated by proteasome-associated degradation but not autophagic degradation. ApoB was degraded by the 20S proteasome in a ubiquitin-independent manner. HCV induced the oxidation of ApoB via oxidative stress, and oxidized ApoB was recognized by the PSMA5 and PSMA6 subunits of the 20S proteasome for degradation. Further study showed that ApoB was degraded at endoplasmic reticulum (ER)-associated lipid droplets (LDs) and that the retrotranslocation and degradation of ApoB required Derlin-1 but not gp78 or p97. Moreover, we found that knockdown of ApoB before infection increased the cellular lipid content and enhanced HCV assembly. Overexpression of ApoB-50 inhibited lipid accumulation and repressed viral assembly in HCV-infected cells. Our study reveals a novel mechanism of ApoB degradation and lipid accumulation during HCV infection and might suggest new therapeutic strategies for hepatic steatosis.Bei WangYue ZhuCongci YuChongyang ZhangQing TangHe HuangZhendong ZhaoPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009889 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Bei Wang Yue Zhu Congci Yu Chongyang Zhang Qing Tang He Huang Zhendong Zhao Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.
description	Hepatitis C virus (HCV) infection induces the degradation and decreases the secretion of apolipoprotein B (ApoB). Impaired production and secretion of ApoB-containing lipoprotein is associated with an increase in hepatic steatosis. Therefore, HCV infection-induced degradation of ApoB may contribute to hepatic steatosis and decreased lipoprotein secretion, but the mechanism of HCV infection-induced ApoB degradation has not been completely elucidated. In this study, we found that the ApoB level in HCV-infected cells was regulated by proteasome-associated degradation but not autophagic degradation. ApoB was degraded by the 20S proteasome in a ubiquitin-independent manner. HCV induced the oxidation of ApoB via oxidative stress, and oxidized ApoB was recognized by the PSMA5 and PSMA6 subunits of the 20S proteasome for degradation. Further study showed that ApoB was degraded at endoplasmic reticulum (ER)-associated lipid droplets (LDs) and that the retrotranslocation and degradation of ApoB required Derlin-1 but not gp78 or p97. Moreover, we found that knockdown of ApoB before infection increased the cellular lipid content and enhanced HCV assembly. Overexpression of ApoB-50 inhibited lipid accumulation and repressed viral assembly in HCV-infected cells. Our study reveals a novel mechanism of ApoB degradation and lipid accumulation during HCV infection and might suggest new therapeutic strategies for hepatic steatosis.
format	article
author	Bei Wang Yue Zhu Congci Yu Chongyang Zhang Qing Tang He Huang Zhendong Zhao
author_facet	Bei Wang Yue Zhu Congci Yu Chongyang Zhang Qing Tang He Huang Zhendong Zhao
author_sort	Bei Wang
title	Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.
title_short	Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.
title_full	Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.
title_fullStr	Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.
title_full_unstemmed	Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.
title_sort	hepatitis c virus induces oxidation and degradation of apolipoprotein b to enhance lipid accumulation and promote viral production.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/63f99eb007dd407484c4dbb557f0498d
work_keys_str_mv	AT beiwang hepatitiscvirusinducesoxidationanddegradationofapolipoproteinbtoenhancelipidaccumulationandpromoteviralproduction AT yuezhu hepatitiscvirusinducesoxidationanddegradationofapolipoproteinbtoenhancelipidaccumulationandpromoteviralproduction AT congciyu hepatitiscvirusinducesoxidationanddegradationofapolipoproteinbtoenhancelipidaccumulationandpromoteviralproduction AT chongyangzhang hepatitiscvirusinducesoxidationanddegradationofapolipoproteinbtoenhancelipidaccumulationandpromoteviralproduction AT qingtang hepatitiscvirusinducesoxidationanddegradationofapolipoproteinbtoenhancelipidaccumulationandpromoteviralproduction AT hehuang hepatitiscvirusinducesoxidationanddegradationofapolipoproteinbtoenhancelipidaccumulationandpromoteviralproduction AT zhendongzhao hepatitiscvirusinducesoxidationanddegradationofapolipoproteinbtoenhancelipidaccumulationandpromoteviralproduction
_version_	1718375725837320192

Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.

Ejemplares similares