Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production.

Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of enveloped DNA viruses. It was previously shown that HBV can induce endoplasmic reticulum (ER) stress and activate the IRE1-XBP1 pathway of the unfolded protein response (UPR), through the expression of the viral regulatory protein X (HB...

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Autores principales:	Catalin Lazar, Alina Macovei, Stefana Petrescu, Norica Branza-Nichita
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eb1f9ce9004744e6b3898e8de911feb6
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spelling	oai:doaj.org-article:eb1f9ce9004744e6b3898e8de911feb62021-11-18T07:24:19ZActivation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production.1932-620310.1371/journal.pone.0034169https://doaj.org/article/eb1f9ce9004744e6b3898e8de911feb62012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22461906/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of enveloped DNA viruses. It was previously shown that HBV can induce endoplasmic reticulum (ER) stress and activate the IRE1-XBP1 pathway of the unfolded protein response (UPR), through the expression of the viral regulatory protein X (HBx). However, it remained obscure whether or not this activation had any functional consequences on the target genes of the UPR pathway. Of these targets, the ER degradation-enhancing, mannosidase-like proteins (EDEMs) are thought to play an important role in relieving the ER stress during UPR, by recognizing terminally misfolded glycoproteins and delivering them to the ER-associated degradation (ERAD). In this study, we investigated the role of EDEMs in the HBV life-cycle. We found that synthesis of EDEMs (EDEM1 and its homologues, EDEM2 and EDEM3) is significantly up-regulated in cells with persistent or transient HBV replication. Co-expression of the wild-type HBV envelope proteins with EDEM1 resulted in their massive degradation, a process reversed by EDEM1 silencing. Surprisingly, the autophagy/lysosomes, rather than the proteasome were involved in disposal of the HBV envelope proteins. Importantly, inhibition of the endogenous EDEM1 expression in HBV replicating cells significantly increased secretion of both, enveloped virus and subviral particles. This is the first report showing that HBV activates the ERAD pathway, which, in turn, reduces the amount of envelope proteins, possibly as a mechanism to control the level of virus particles in infected cells and facilitate the establishment of chronic infections.Catalin LazarAlina MacoveiStefana PetrescuNorica Branza-NichitaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e34169 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Catalin Lazar Alina Macovei Stefana Petrescu Norica Branza-Nichita Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production.
description	Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of enveloped DNA viruses. It was previously shown that HBV can induce endoplasmic reticulum (ER) stress and activate the IRE1-XBP1 pathway of the unfolded protein response (UPR), through the expression of the viral regulatory protein X (HBx). However, it remained obscure whether or not this activation had any functional consequences on the target genes of the UPR pathway. Of these targets, the ER degradation-enhancing, mannosidase-like proteins (EDEMs) are thought to play an important role in relieving the ER stress during UPR, by recognizing terminally misfolded glycoproteins and delivering them to the ER-associated degradation (ERAD). In this study, we investigated the role of EDEMs in the HBV life-cycle. We found that synthesis of EDEMs (EDEM1 and its homologues, EDEM2 and EDEM3) is significantly up-regulated in cells with persistent or transient HBV replication. Co-expression of the wild-type HBV envelope proteins with EDEM1 resulted in their massive degradation, a process reversed by EDEM1 silencing. Surprisingly, the autophagy/lysosomes, rather than the proteasome were involved in disposal of the HBV envelope proteins. Importantly, inhibition of the endogenous EDEM1 expression in HBV replicating cells significantly increased secretion of both, enveloped virus and subviral particles. This is the first report showing that HBV activates the ERAD pathway, which, in turn, reduces the amount of envelope proteins, possibly as a mechanism to control the level of virus particles in infected cells and facilitate the establishment of chronic infections.
format	article
author	Catalin Lazar Alina Macovei Stefana Petrescu Norica Branza-Nichita
author_facet	Catalin Lazar Alina Macovei Stefana Petrescu Norica Branza-Nichita
author_sort	Catalin Lazar
title	Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production.
title_short	Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production.
title_full	Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production.
title_fullStr	Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production.
title_full_unstemmed	Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production.
title_sort	activation of erad pathway by human hepatitis b virus modulates viral and subviral particle production.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/eb1f9ce9004744e6b3898e8de911feb6
work_keys_str_mv	AT catalinlazar activationoferadpathwaybyhumanhepatitisbvirusmodulatesviralandsubviralparticleproduction AT alinamacovei activationoferadpathwaybyhumanhepatitisbvirusmodulatesviralandsubviralparticleproduction AT stefanapetrescu activationoferadpathwaybyhumanhepatitisbvirusmodulatesviralandsubviralparticleproduction AT noricabranzanichita activationoferadpathwaybyhumanhepatitisbvirusmodulatesviralandsubviralparticleproduction
_version_	1718423507038109696

Activation of ERAD pathway by human hepatitis B virus modulates viral and subviral particle production.

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