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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2018
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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 |
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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 |
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