Next Article in Journal
Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments
Next Article in Special Issue
HPV Population Profiling in Healthy Men by Next-Generation Deep Sequencing Coupled with HPV-QUEST
Previous Article in Journal
Innate Immunity Evasion by Enteroviruses: Insights into Virus-Host Interaction
Previous Article in Special Issue
Quantifying Next Generation Sequencing Sample Pre-Processing Bias in HIV-1 Complete Genome Sequencing
Article Menu

Export Article

Open AccessArticle
Viruses 2016, 8(1), 19; doi:10.3390/v8010019

Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection

1
Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, University of London, London WC1E 7HT, UK
2
Institute of Cardiac diagnostics (IKDT), Charite University, D-12203 Berlin, Germany
Current address: Department of Archeogenetics, Max Planck Institute for the Science of Human History, Jena, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Johnson Mak, Peter Walker and Marcus Thomas Gilbert
Received: 7 October 2015 / Revised: 25 November 2015 / Accepted: 1 December 2015 / Published: 15 January 2016
View Full-Text   |   Download PDF [1436 KB, uploaded 15 January 2016]   |  

Abstract

Human herpesvirus-6A and B (HHV-6A, HHV-6B) have recently defined endogenous genomes, resulting from integration into the germline: chromosomally-integrated “CiHHV-6A/B”. These affect approximately 1.0% of human populations, giving potential for virus gene expression in every cell. We previously showed that CiHHV-6A was more divergent than CiHHV-6B by examining four genes in 44 European CiHHV-6A/B cardiac/haematology patients. There was evidence for gene expression/reactivation, implying functional non-defective genomes. To further define the relationship between HHV-6A and CiHHV-6A we used next-generation sequencing to characterize genomes from three CiHHV-6A cardiac patients. Comparisons to known exogenous HHV-6A showed CiHHV-6A genomes formed a separate clade; including all 85 non-interrupted genes and necessary cis-acting signals for reactivation as infectious virus. Greater single nucleotide polymorphism (SNP) density was defined in 16 genes and the direct repeats (DR) terminal regions. Using these SNPs, deep sequencing analyses demonstrated superinfection with exogenous HHV-6A in two of the CiHHV-6A patients with recurrent cardiac disease. Characterisation of the integration sites in twelve patients identified the human chromosome 17p subtelomere as a prevalent site, which had specific repeat structures and phylogenetically related CiHHV-6A coding sequences indicating common ancestral origins. Overall CiHHV-6A genomes were similar, but distinct from known exogenous HHV-6A virus, and have the capacity to reactivate as emerging virus infections. View Full-Text
Keywords: chromosomal integration; human herpesvirus; HHV-6; CiHHV-6; HHV-6A; CiHHV-6A; subtelomere; virus genome; telomeric repeats chromosomal integration; human herpesvirus; HHV-6; CiHHV-6; HHV-6A; CiHHV-6A; subtelomere; virus genome; telomeric repeats
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Tweedy, J.; Spyrou, M.A.; Pearson, M.; Lassner, D.; Kuhl, U.; Gompels, U.A. Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection. Viruses 2016, 8, 19.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top