Variation in human herpesvirus 6B telomeric integration, excision, and transmission between tissues and individuals.
excision
genetics
genomics
human herpesvirus 6
infectious disease
integration
latency
microbiology
telomere
viruses
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
21 09 2021
21 09 2021
Historique:
received:
17
05
2021
accepted:
20
09
2021
pubmed:
22
9
2021
medline:
19
1
2022
entrez:
21
9
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34545807
doi: 10.7554/eLife.70452
pii: 70452
pmc: PMC8492063
doi:
pii:
Substances chimiques
DNA, Viral
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : G0901657
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12014/3
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : MIBTP 1645656
Pays : United Kingdom
Organisme : CIHR
ID : MOP 123214
Pays : Canada
Informations de copyright
© 2021, Wood et al.
Déclaration de conflit d'intérêts
MW, CV, RN, NS, JN, AP, DM, SR, VC, NS, AV, MT, LF, AD, NR No competing interests declared
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