ArticlePLoS pathogens2016
The Telomeric Repeats of Human Herpesvirus 6A (HHV-6A) Are Required for Efficient Virus Integration.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 71 citations in OpenAlex.
- A Patient-Derived iPSC-Based Model Reveals Neural Lineage-Specific Transcription of Endogenous HHV-6B.The Journal of infectious diseases · 2026Article
- Human herpesvirus 7 integrates into host telomeres via its telomeric repeat arrays.PLoS pathogens · 2026Article
- Article
- Identification of stimuli that enhance human herpesvirus 6A (HHV-6A) replication and reconstitution.Journal of virology · 2024Article
- Telomeric repeats in the commercial SB-1 vaccine facilitate viral integration and contribute to vaccine efficacy.NPJ vaccines · 2024Article
- Impact of viral telomeric repeat sequences on herpesvirus vector vaccine integration and persistence.PLoS pathogens · 2024Article
- The immediate-early protein 1 of human herpesvirus 6B interacts with NBS1 and inhibits ATM signaling.EMBO reports · 2024Article
- The Telomeric Repeats of HHV-6A Do Not Determine the Chromosome into Which the Virus Is Integrated.Genes · 2023Article
- Investigation of a herpesvirus outbreak in mixed breeds of adult domestic ducks using next generation sequencing.PloS one · 2023Article
- Transmission dynamics of human herpesvirus 6A, 6B and 7 from whole genome sequences of families.Virology journal · 2022Article
- The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development.Cancers · 2022Review
- Impact of Host Telomere Length on HHV-6 Integration.Viruses · 2022Article
- Article
- A Cell Culture System to Investigate Marek's Disease Virus Integration into Host Chromosomes.Microorganisms · 2021Article
- Article
- Evasion of the Host Immune Response by Betaherpesviruses.International journal of molecular sciences · 2021Review
- Left-handed DNA-PAINT for improved super-resolution imaging in the nucleus.Nature biotechnology · 2021Article
- Evolutionary History of Endogenous Human Herpesvirus 6 Reflects Human Migration out of Africa.Molecular biology and evolution · 2021Article
- Higher-Order Chromatin Structures of Chromosomally Integrated HHV-6A Predict Integration Sites.Frontiers in cellular and infection microbiology · 2021Article
- Unbiased optical mapping of telomere-integrated endogenous human herpesvirus 6.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are ubiquitous betaherpesviruses that infects humans within the first years of life and establishes latency in various cell types. Both viruses can integrate their genomes into telomeres of host chromosomes in latently infected cells. The molecular mechanism of viral integration remains elusive. Intriguingly, HHV-6A, HHV-6B and several other herpesviruses harbor arrays of telomeric repeats (TMR) identical to human telomere sequences at the ends of their genomes. The HHV-6A and HHV-6B genomes harbor two TMR arrays, the perfect TMR (pTMR) and the imperfect TMR (impTMR). To determine if the TMR are involved in virus integration, we deleted both pTMR and impTMR in the HHV-6A genome. Upon reconstitution, the TMR mutant virus replicated comparable to wild type (wt) virus, indicating that the TMR are not essential for HHV-6A replication. To assess the integration properties of the recombinant viruses, we established an in vitro integration system that allows assessment of integration efficiency and genome maintenance in latently infected cells. Integration of HHV-6A was severely impaired in the absence of the TMR and the virus genome was lost rapidly, suggesting that integration is crucial for the maintenance of the virus genome. Individual deletion of the pTMR and impTMR revealed that the pTMR play the major role in HHV-6A integration, whereas the impTMR only make a minor contribution, allowing us to establish a model for HHV-6A integration. Taken together, our data shows that the HHV-6A TMR are dispensable for virus replication, but are crucial for integration and maintenance of the virus genome in latently infected cells.
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