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Endogenous Human Herpesvirus: Germ line integration and effects on host cell and organism

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.

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Keywords

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2022-COG

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Host institution

FREIE UNIVERSITAET BERLIN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 000 000,00
Address
KAISERSWERTHER STRASSE 16-18
14195 BERLIN
Germany

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Region
Berlin Berlin Berlin
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 000 000,00

Beneficiaries (1)

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