Project description
Inherited herpesvirus in the human genome
Viruses have shaped human evolution, and some have permanently embedded their DNA into our genome. One striking example is human herpesvirus 6 (HHV-6), which integrated into the telomeres of germ cells, and is now inherited by about 1 % of the global population. Although usually silent, HHV-6 can reactivate and has been linked to seizures, encephalitis, heart failure and transplant complications. The goal of the ERC-funded ENDo-HERPES project is to investigate which inherited viral genomes remain functional and how they integrate and reactivate within telomeres. Using advanced genomic technologies, the project will clarify whether and how this embedded virus contributes to human disease and whether it is influenced by ageing-related telomere shortening.
Objective
Endogenous viruses present in the human genome control physiological processes, modulate aging, and can cause diseases. Intriguingly, a herpesvirus has entered the human germ line by integrating its genome into telomeres of germ cells and is present in about 80 million people. The virus, human herpesvirus 6 (HHV-6), can reactivate from the integrated state, which is associated with a number of diseases. These include seizures, encephalitis, heart failure and graft rejection. We recently analysed the virus genomes present in hundreds of individuals with this inherited chromosomally-integrated HHV-6 (iciHHV-6). The data show that todays endogenous virus sequences are quite diverse and derived from dozens of independent integration events that were passed on for generations. There are critical gaps in our knowledge on the functionality of iciHHV-6 genomes with respect to virus replication, gene expression and latency, its effects on the host cell, and the role of telomere shortening that occurs during aging on virus reactivation. ENDo-HERPES will make use of novel technology to close these gaps and provide the basis for elucidating whether diseases are associated with or caused by iciHHV-6. Specifically, we will 1) identify which iciHHV-6 genomes are still functional and could contribute to disease development; 2) determine iciHHV-6 integration sites within the highly repetitive telomere region and assess the integration and reactivation process on the DNA level; and 3) investigate the effects of the iciHHV-6 genome on host cells and if telomere shortening can induce reactivation. The proposal utilizes state-of-the-art technology and pioneers new approaches, particularly when investigating the integration sites of endogenous virus genomes and the mechanisms facilitating integration and reactivation. Altogether, we will shed light on the life cycle and effects on the host cells of this endogenous herpesvirus present in the genome of about 1% of the human population.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics genomes
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2022-COG
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14195 Berlin
Germany
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