Cargando…

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

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 repli...

Descripción completa

Detalles Bibliográficos
Autores principales: Ding, Qiang, Nimgaonkar, Ila, Archer, Nicholas F., Bram, Yaron, Heller, Brigitte, Schwartz, Robert E., Ploss, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941075/
https://www.ncbi.nlm.nih.gov/pubmed/29739903
http://dx.doi.org/10.1128/mBio.00769-18
_version_ 1783321221493948416
author Ding, Qiang
Nimgaonkar, Ila
Archer, Nicholas F.
Bram, Yaron
Heller, Brigitte
Schwartz, Robert E.
Ploss, Alexander
author_facet Ding, Qiang
Nimgaonkar, Ila
Archer, Nicholas F.
Bram, Yaron
Heller, Brigitte
Schwartz, Robert E.
Ploss, Alexander
author_sort Ding, Qiang
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5941075
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-59410752018-05-15 Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription Ding, Qiang Nimgaonkar, Ila Archer, Nicholas F. Bram, Yaron Heller, Brigitte Schwartz, Robert E. Ploss, Alexander mBio Research Article 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. American Society for Microbiology 2018-05-08 /pmc/articles/PMC5941075/ /pubmed/29739903 http://dx.doi.org/10.1128/mBio.00769-18 Text en Copyright © 2018 Ding et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Ding, Qiang
Nimgaonkar, Ila
Archer, Nicholas F.
Bram, Yaron
Heller, Brigitte
Schwartz, Robert E.
Ploss, Alexander
Identification of the Intragenomic Promoter Controlling Hepatitis E Virus Subgenomic RNA Transcription
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941075/
https://www.ncbi.nlm.nih.gov/pubmed/29739903
http://dx.doi.org/10.1128/mBio.00769-18
work_keys_str_mv AT dingqiang identificationoftheintragenomicpromotercontrollinghepatitisevirussubgenomicrnatranscription
AT nimgaonkarila identificationoftheintragenomicpromotercontrollinghepatitisevirussubgenomicrnatranscription
AT archernicholasf identificationoftheintragenomicpromotercontrollinghepatitisevirussubgenomicrnatranscription
AT bramyaron identificationoftheintragenomicpromotercontrollinghepatitisevirussubgenomicrnatranscription
AT hellerbrigitte identificationoftheintragenomicpromotercontrollinghepatitisevirussubgenomicrnatranscription
AT schwartzroberte identificationoftheintragenomicpromotercontrollinghepatitisevirussubgenomicrnatranscription
AT plossalexander identificationoftheintragenomicpromotercontrollinghepatitisevirussubgenomicrnatranscription