Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals

Human herpesviruses 6A and 6B (HHV-6A/6B) are ubiquitous pathogens that persist lifelong in latent form and can cause severe conditions upon reactivation. They are spread by community-acquired infection of free virus (acqHHV6A/6B) and by germline transmission of inherited chromosomally integrated HH...

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Autores principales:	Michael L Wood, Colin D Veal, Rita Neumann, Nicolás M Suárez, Jenna Nichols, Andrei J Parker, Diana Martin, Simon PR Romaine, Veryan Codd, Nilesh J Samani, Adriaan A Voors, Maciej Tomaszewski, Louis Flamand, Andrew J Davison, Nicola J Royle
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	excision integration human herpesvirus 6 latency telomere Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/739e0ec094364dfd9c2de17914d4c097
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spelling	oai:doaj.org-article:739e0ec094364dfd9c2de17914d4c0972021-12-01T10:59:37ZVariation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals10.7554/eLife.704522050-084Xe70452https://doaj.org/article/739e0ec094364dfd9c2de17914d4c0972021-09-01T00:00:00Zhttps://elifesciences.org/articles/70452https://doaj.org/toc/2050-084XHuman herpesviruses 6A and 6B (HHV-6A/6B) are ubiquitous pathogens that persist lifelong in latent form and can cause severe conditions upon reactivation. They are spread by community-acquired infection of free virus (acqHHV6A/6B) and by germline transmission of inherited chromosomally integrated HHV-6A/6B (iciHHV-6A/6B) in telomeres. We exploited a hypervariable region of the HHV-6B genome to investigate the relationship between acquired and inherited virus and revealed predominantly maternal transmission of acqHHV-6B in families. Remarkably, we demonstrate that some copies of acqHHV-6B in saliva from healthy adults gained a telomere, indicative of integration and latency, and that the frequency of viral genome excision from telomeres in iciHHV-6B carriers is surprisingly high and varies between tissues. In addition, newly formed short telomeres generated by partial viral genome release are frequently lengthened, particularly in telomerase-expressing pluripotent cells. Consequently, iciHHV-6B carriers are mosaic for different iciHHV-6B structures, including circular extra-chromosomal forms that have the potential to reactivate. Finally, we show transmission of an HHV-6B strain from an iciHHV-6B mother to her non-iciHHV-6B son. Altogether, we demonstrate that iciHHV-6B can readily transition between telomere-integrated and free virus forms.Michael L WoodColin D VealRita NeumannNicolás M SuárezJenna NicholsAndrei J ParkerDiana MartinSimon PR RomaineVeryan CoddNilesh J SamaniAdriaan A VoorsMaciej TomaszewskiLouis FlamandAndrew J DavisonNicola J RoyleeLife Sciences Publications Ltdarticleexcisionintegrationhuman herpesvirus 6latencytelomereMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	excision integration human herpesvirus 6 latency telomere Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	excision integration human herpesvirus 6 latency telomere Medicine R Science Q Biology (General) QH301-705.5 Michael L Wood Colin D Veal Rita Neumann Nicolás M Suárez Jenna Nichols Andrei J Parker Diana Martin Simon PR Romaine Veryan Codd Nilesh J Samani Adriaan A Voors Maciej Tomaszewski Louis Flamand Andrew J Davison Nicola J Royle Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals
description	Human herpesviruses 6A and 6B (HHV-6A/6B) are ubiquitous pathogens that persist lifelong in latent form and can cause severe conditions upon reactivation. They are spread by community-acquired infection of free virus (acqHHV6A/6B) and by germline transmission of inherited chromosomally integrated HHV-6A/6B (iciHHV-6A/6B) in telomeres. We exploited a hypervariable region of the HHV-6B genome to investigate the relationship between acquired and inherited virus and revealed predominantly maternal transmission of acqHHV-6B in families. Remarkably, we demonstrate that some copies of acqHHV-6B in saliva from healthy adults gained a telomere, indicative of integration and latency, and that the frequency of viral genome excision from telomeres in iciHHV-6B carriers is surprisingly high and varies between tissues. In addition, newly formed short telomeres generated by partial viral genome release are frequently lengthened, particularly in telomerase-expressing pluripotent cells. Consequently, iciHHV-6B carriers are mosaic for different iciHHV-6B structures, including circular extra-chromosomal forms that have the potential to reactivate. Finally, we show transmission of an HHV-6B strain from an iciHHV-6B mother to her non-iciHHV-6B son. Altogether, we demonstrate that iciHHV-6B can readily transition between telomere-integrated and free virus forms.
format	article
author	Michael L Wood Colin D Veal Rita Neumann Nicolás M Suárez Jenna Nichols Andrei J Parker Diana Martin Simon PR Romaine Veryan Codd Nilesh J Samani Adriaan A Voors Maciej Tomaszewski Louis Flamand Andrew J Davison Nicola J Royle
author_facet	Michael L Wood Colin D Veal Rita Neumann Nicolás M Suárez Jenna Nichols Andrei J Parker Diana Martin Simon PR Romaine Veryan Codd Nilesh J Samani Adriaan A Voors Maciej Tomaszewski Louis Flamand Andrew J Davison Nicola J Royle
author_sort	Michael L Wood
title	Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals
title_short	Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals
title_full	Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals
title_fullStr	Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals
title_full_unstemmed	Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals
title_sort	variation in human herpesvirus 6b telomeric integration, excision, and transmission between tissues and individuals
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/739e0ec094364dfd9c2de17914d4c097
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Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals

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