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

Wood, M. L. et al. (2021) Variation in human herpesvirus 6B telomeric integration, excision and transmission between tissues and individuals. eLife, 10, e70452. (doi: 10.7554/eLife.70452) (PMID:34545807) (PMCID:PMC8492063)

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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.

Item Type:Articles
Additional Information:MLW was funded UK Biotechnology and Biological Sciences Research Council (BBSRC) and the Midlands Integrative Biosciences Training Partnership (MIBTP 1645656). The work was supported in part by the UK Medical Research Council (G0901657 to N.J.R. and MC_UU_12014/3 to A.J.D.); HHV-6 Foundation pilot grant to NJR; the Canadian Institutes of Health Research grants (MOP_123214) to LF. The BIOSTAT-CHF project was funded by a grant from the European Commission (FP7-242209- BIOSTAT-CHF).
Glasgow Author(s) Enlighten ID:Davison, Professor Andrew and Suarez, Dr Nicolas and Nichols, Mrs Jenna and Wood, Dr Michael
Authors: Wood, M. L., Veal, C. D., Neumann, R., Suarez, N. M., Nichols, J., Parker, A. J., Martin, D., Romaine, S. P.R., Codd, V., Samani, N. J., Voors, A. A., Tomaszewski, M., Flamand, L., Davison, A. J., and Royle, N. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN (Online):2050-084X
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in eLife 10:e70452
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656321Genomics of human cytomegalovirusAndrew DavisonMedical Research Council (MRC)MC_UU_12014/3MVLS III - CENTRE FOR VIRUS RESEARCH