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dc.contributor.authorRomaine, Simon
dc.contributor.authorSamani, Nilesh
dc.date.accessioned2022-01-28T15:19:29Z
dc.date.available2022-01-28T15:19:29Z
dc.date.issued2021
dc.identifier.citationWood, M. L., Veal, C. D., Neumann, R., Suárez, N. M., Nichols, J., Parker, A. J., Martin, D., Romaine, S. P., Codd, V., Samani, N. J., Voors, A. A., Tomaszewski, M., Flamand, L., Davison, A. J., & Royle, N. J. (2021). Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals. eLife, 10, e70452. https://doi.org/10.7554/eLife.70452en_US
dc.identifier.urihttp://hdl.handle.net/20.500.12904/15129
dc.description.abstractHuman 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.
dc.description.urihttps://elifesciences.org/articles/70452en_US
dc.language.isoenen_US
dc.subjectexcisionen_US
dc.subjectgeneticsen_US
dc.subjectgenomicsen_US
dc.subjecthuman herpesvirus 6en_US
dc.subjectinfectious diseaseen_US
dc.subjectintegrationen_US
dc.subjectlatencyen_US
dc.subjectmicrobiologyen_US
dc.subjecttelomereen_US
dc.subjectvirusesen_US
dc.titleVariation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individualsen_US
dc.typeArticleen_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US
rioxxterms.versionVoRen_US
rioxxterms.versionofrecordhttps://doi.org/10.7554/eLife.70452en_US
rioxxterms.typeJournal Article/Reviewen_US
refterms.dateFCD2022-01-28T15:19:29Z
refterms.versionFCDVoR
refterms.dateFOA2022-01-28T15:19:29Z
refterms.panelUnspecifieden_US
refterms.dateFirstOnline2021-09
html.description.abstractHuman 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.en_US
rioxxterms.funder.project94a427429a5bcfef7dd04c33360d80cden_US


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