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Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites

Human herpesvirus -6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes. Viral integration can occur in several cell types, including germinal cells, resulting in individuals that harbor the viral genome in every cell of their body. The integrated genome is effici...

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Autores principales: Mariani, Michael, Zimmerman, Cosima, Rodriguez, Princess, Hasenohr, Ellie, Aimola, Giulia, Gerrard, Diana Lea, Richman, Alyssa, Dest, Andrea, Flamand, Louis, Kaufer, Benedikt, Frietze, Seth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953476/
https://www.ncbi.nlm.nih.gov/pubmed/33718266
http://dx.doi.org/10.3389/fcimb.2021.612656
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author Mariani, Michael
Zimmerman, Cosima
Rodriguez, Princess
Hasenohr, Ellie
Aimola, Giulia
Gerrard, Diana Lea
Richman, Alyssa
Dest, Andrea
Flamand, Louis
Kaufer, Benedikt
Frietze, Seth
author_facet Mariani, Michael
Zimmerman, Cosima
Rodriguez, Princess
Hasenohr, Ellie
Aimola, Giulia
Gerrard, Diana Lea
Richman, Alyssa
Dest, Andrea
Flamand, Louis
Kaufer, Benedikt
Frietze, Seth
author_sort Mariani, Michael
collection PubMed
description Human herpesvirus -6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes. Viral integration can occur in several cell types, including germinal cells, resulting in individuals that harbor the viral genome in every cell of their body. The integrated genome is efficiently silenced but can sporadically reactivate resulting in various clinical symptoms. To date, the integration mechanism and the subsequent silencing of HHV-6A/B genes remains poorly understood. Here we investigate the genome-wide chromatin contacts of the integrated HHV-6A in latently-infected cells. We show that HHV-6A becomes transcriptionally silent upon infection of these cells over the course of seven days. In addition, we established an HHV-6–specific 4C-seq approach, revealing that the HHV-6A 3D interactome is associated with quiescent chromatin states in cells harboring integrated virus. Furthermore, we observed that the majority of virus chromatin interactions occur toward the distal ends of specific human chromosomes. Exploiting this finding, we established a 4C-seq method that accurately detects the chromosomal integration sites. We further implement long-read minION sequencing in the 4C-seq assay and developed a method to identify HHV-6A/B integration sites in clinical samples.
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spelling pubmed-79534762021-03-13 Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites Mariani, Michael Zimmerman, Cosima Rodriguez, Princess Hasenohr, Ellie Aimola, Giulia Gerrard, Diana Lea Richman, Alyssa Dest, Andrea Flamand, Louis Kaufer, Benedikt Frietze, Seth Front Cell Infect Microbiol Cellular and Infection Microbiology Human herpesvirus -6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of human chromosomes. Viral integration can occur in several cell types, including germinal cells, resulting in individuals that harbor the viral genome in every cell of their body. The integrated genome is efficiently silenced but can sporadically reactivate resulting in various clinical symptoms. To date, the integration mechanism and the subsequent silencing of HHV-6A/B genes remains poorly understood. Here we investigate the genome-wide chromatin contacts of the integrated HHV-6A in latently-infected cells. We show that HHV-6A becomes transcriptionally silent upon infection of these cells over the course of seven days. In addition, we established an HHV-6–specific 4C-seq approach, revealing that the HHV-6A 3D interactome is associated with quiescent chromatin states in cells harboring integrated virus. Furthermore, we observed that the majority of virus chromatin interactions occur toward the distal ends of specific human chromosomes. Exploiting this finding, we established a 4C-seq method that accurately detects the chromosomal integration sites. We further implement long-read minION sequencing in the 4C-seq assay and developed a method to identify HHV-6A/B integration sites in clinical samples. Frontiers Media S.A. 2021-02-26 /pmc/articles/PMC7953476/ /pubmed/33718266 http://dx.doi.org/10.3389/fcimb.2021.612656 Text en Copyright © 2021 Mariani, Zimmerman, Rodriguez, Hasenohr, Aimola, Gerrard, Richman, Dest, Flamand, Kaufer and Frietze http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Mariani, Michael
Zimmerman, Cosima
Rodriguez, Princess
Hasenohr, Ellie
Aimola, Giulia
Gerrard, Diana Lea
Richman, Alyssa
Dest, Andrea
Flamand, Louis
Kaufer, Benedikt
Frietze, Seth
Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites
title Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites
title_full Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites
title_fullStr Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites
title_full_unstemmed Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites
title_short Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites
title_sort higher-order chromatin structures of chromosomally integrated hhv-6a predict integration sites
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953476/
https://www.ncbi.nlm.nih.gov/pubmed/33718266
http://dx.doi.org/10.3389/fcimb.2021.612656
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