Approved Research

Inherited chromosomally-integrated human herpesvirus 6 (iciHHV-6): associations with disease and phenotype

Lay summary

Almost one million individuals in the UK have inherited chromosomally-integrated human herpesvirus 6 (iciHHV-6) but little is known of the consequences. Individuals with iciHHV-6 have the genetic material, or genome, of human herpesvirus 6 in every cell of their body, and transmit the virus to offspring in sperm or ova.  The viral genome is present within telomeres, structures which protect chromosome ends and have been likened to the plastic tips at the end of shoelaces. Shortening of telomeres is a recognised marker of biological ageing, and contributes to age-related diseases.  Recent data show that iciHHV-6 genomes can be released from telomeres. This is associated with sudden telomere shortening and can lead to viral reactivation with production of infectious virus.  Case studies provide evidence that viral reactivation does occur in iciHHV-6+ people, and that release of viral genomes may play a role in the development of cancer; however, the frequency of these events is not clear.  Analysis of two cohort studies also revealed an unexpected, although plausible, association between iciHHV-6 and angina. Thus, iciHHV-6 is not simply a fossilised viral remnant, but can cause disease.   The aim of this study is to investigate the impact of iciHHV-6 on health and well-being.  We will look for novel disease associations with iciHHV-6 and investigate the association with angina, and related cardiovascular diseases, in detail.

We will perform the project over four years.  We will first screen DNA samples from UK Biobank participants for iciHHV-6 using state-of-the-art tests, optimised in our laboratory.  In the second part of the project, statistical analysis will be performed to identify associations between iciHHV-6 and information held by UK Biobank on a wide range of diseases and physical characteristics.  The study will determine whether iciHHV-6 is medically important.  Identification of diseases caused by iciHHV-6 will ultimately lead to improved diagnostic accuracy and treatment decisions for those with iciHHV-6.  Identification of iciHHV-6 as a risk factor for common conditions, such as angina, may lead to improved prediction of disease risk thus providing patients with more information.  If iciHHV-6 is found to be mostly harmless, this will provide an important evidence base for reassuring individuals who are iciHHV-6+.  Information on iciHHV-6 status will also augment the genetic data held within UK Biobank.

Scope extension:

New scope: The 'new scope' fits the previous scope; the request is to change the methodology and involve a commercial organisation. We seek approval for BioClavis (https://www.bioclavis.co.uk/) to perform a custom TempO-Seq® analysis of the iciHHV-6-positive samples identified in Stage 1 of our project. BioClavis is a Glasgow-based company providing analysis using the TempO-Seq® platform, developed by its parent company BioSpyder. Using TempO-Seq®, we will extend the characterisation of viral genomes and improve our ability to identify ancestral iciHHV-6 viral lineages.

A small aliquot of DNA from iciHHV-6 positive samples (n=6000) will be sent to BioClavis. We will retain DNA from all samples, and BioClavis will return residual DNA; therefore, no samples will be exhausted using the TempO-Seq® assay. Samples will be labelled using our laboratory identifiers, and we will not send any other data to BioClavis. An MTA and Service Agreement between the University of Glasgow and BioClavis are in place.