Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription

ABSTRACT Approximately 20 million hepatitis E virus (HEV) infections occur annually in both developing and industrialized countries. Most infections are self-limiting, but they can lead to chronic infections and cirrhosis in immunocompromised patients, and death in pregnant women. The mechanisms of...

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Autores principales:	Qiang Ding, Ila Nimgaonkar, Nicholas F. Archer, Yaron Bram, Brigitte Heller, Robert E. Schwartz, Alexander Ploss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	hepatitis E hepatitis E virus viral hepatitis viral replication Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/da759183b0e640e6bcb3f00ec4984c76
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spelling	oai:doaj.org-article:da759183b0e640e6bcb3f00ec4984c762021-11-15T16:00:26ZIdentification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription10.1128/mBio.00769-182150-7511https://doaj.org/article/da759183b0e640e6bcb3f00ec4984c762018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00769-18https://doaj.org/toc/2150-7511ABSTRACT Approximately 20 million hepatitis E virus (HEV) infections occur annually in both developing and industrialized countries. Most infections are self-limiting, but they can lead to chronic infections and cirrhosis in immunocompromised patients, and death in pregnant women. The mechanisms of HEV replication remain incompletely understood due to scarcity of adequate experimental platforms. HEV undergoes asymmetric genome replication, but it produces an additional subgenomic (SG) RNA encoding the viral capsid and a viroporin in partially overlapping open reading frames. Using a novel transcomplementation system, we mapped the intragenomic subgenomic promoter regulating SG RNA synthesis. This cis-acting element is highly conserved across all eight HEV genotypes, and when the element is mutated, it abrogates particle assembly and release. Our work defines previously unappreciated viral regulatory elements and provides the first in-depth view of the intracellular genome dynamics of this emerging human pathogen. IMPORTANCE HEV is an emerging pathogen causing severe liver disease. The genetic information of HEV is encoded in RNA. The genomic RNA is initially copied into a complementary, antigenomic RNA that is a template for synthesis of more genomic RNA and for so-called subgenomic RNA. In this study, we identified the precise region within the HEV genome at which the synthesis of the subgenomic RNA is initiated. The nucleotides within this region are conserved across genetically distinct variants of HEV, highlighting the general importance of this segment for the virus. To identify this regulatory element, we developed a new experimental system that is a powerful tool with broad utility to mechanistically dissect many other poorly understood functional elements of HEV.Qiang DingIla NimgaonkarNicholas F. ArcherYaron BramBrigitte HellerRobert E. SchwartzAlexander PlossAmerican Society for Microbiologyarticlehepatitis Ehepatitis E virusviral hepatitisviral replicationMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatitis E hepatitis E virus viral hepatitis viral replication Microbiology QR1-502
spellingShingle	hepatitis E hepatitis E virus viral hepatitis viral replication Microbiology QR1-502 Qiang Ding Ila Nimgaonkar Nicholas F. Archer Yaron Bram Brigitte Heller Robert E. Schwartz Alexander Ploss Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription
description	ABSTRACT Approximately 20 million hepatitis E virus (HEV) infections occur annually in both developing and industrialized countries. Most infections are self-limiting, but they can lead to chronic infections and cirrhosis in immunocompromised patients, and death in pregnant women. The mechanisms of HEV replication remain incompletely understood due to scarcity of adequate experimental platforms. HEV undergoes asymmetric genome replication, but it produces an additional subgenomic (SG) RNA encoding the viral capsid and a viroporin in partially overlapping open reading frames. Using a novel transcomplementation system, we mapped the intragenomic subgenomic promoter regulating SG RNA synthesis. This cis-acting element is highly conserved across all eight HEV genotypes, and when the element is mutated, it abrogates particle assembly and release. Our work defines previously unappreciated viral regulatory elements and provides the first in-depth view of the intracellular genome dynamics of this emerging human pathogen. IMPORTANCE HEV is an emerging pathogen causing severe liver disease. The genetic information of HEV is encoded in RNA. The genomic RNA is initially copied into a complementary, antigenomic RNA that is a template for synthesis of more genomic RNA and for so-called subgenomic RNA. In this study, we identified the precise region within the HEV genome at which the synthesis of the subgenomic RNA is initiated. The nucleotides within this region are conserved across genetically distinct variants of HEV, highlighting the general importance of this segment for the virus. To identify this regulatory element, we developed a new experimental system that is a powerful tool with broad utility to mechanistically dissect many other poorly understood functional elements of HEV.
format	article
author	Qiang Ding Ila Nimgaonkar Nicholas F. Archer Yaron Bram Brigitte Heller Robert E. Schwartz Alexander Ploss
author_facet	Qiang Ding Ila Nimgaonkar Nicholas F. Archer Yaron Bram Brigitte Heller Robert E. Schwartz Alexander Ploss
author_sort	Qiang Ding
title	Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription
title_short	Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription
title_full	Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription
title_fullStr	Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription
title_full_unstemmed	Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription
title_sort	identification of the intragenomic promoter controlling hepatitis e virus subgenomic rna transcription
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/da759183b0e640e6bcb3f00ec4984c76
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Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription

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