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INTEGHER SIGNED

Integration of herpesvirus into telomeres: From the mechanism of genome integration and mobilization to therapeutic intervention

Total Cost €

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EC-Contrib. €

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Project "INTEGHER" data sheet

The following table provides information about the project.

Coordinator
FREIE UNIVERSITAET BERLIN 

Organization address
address: KAISERSWERTHER STRASSE 16-18
city: BERLIN
postcode: 14195
website: www.fu-berlin.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 1˙810˙747 €
 EC max contribution 1˙810˙747 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-04-01   to  2021-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FREIE UNIVERSITAET BERLIN DE (BERLIN) coordinator 1˙810˙747.00

Map

 Project objective

Herpesviruses cause serious diseases in humans and animals. After initial lytic infection, herpesviruses establish a quiescent (latent) infection, which allows their persistence in the host for life. We and others recently identified a novel mechanism that allows maintenance of the genome of certain herpesviruses during latency, by integrating their complete genetic material into host telomeres. One of these viruses is human herpesvirus 6 (HHV-6) which is associated with seizures, encephalitis, and graft rejection in transplant patients. Sporadic reactivation of the integrated virus ensures continued evolution of the virus as it spreads to a new cadre of susceptible individuals. There are critical gaps in our knowledge regarding the fate of herpesvirus genomes during integration and reactivation as well as of viral and cellular factors involved in these processes. INTEGHER will make use of novel technologies to close these gaps and to devise new therapeutic approaches. Specifically, we will 1) determine the fate of the HHV-6 genome during latency by developing a novel reporter system that allows live-cell imaging of the virus genome in living cells and elucidate epigenetic changes of the HHV-6 genome during integration and reactivation; 2) identify viral and cellular factors that drive virus genome integration and reactivation, using recombinant viruses, drugs and CRISPR/Cas9 genome engineering 3) employ genome-editing tools to eliminate the virus genome integrated in host chromosomes in vitro and in an in vivo model. The proposal utilizes state-of-the-art technologies and pioneers new approaches, particularly with regard to visualization and excision of virus genomes in latently infected cells that are also present in (bone marrow) transplants. Altogether, these studies will define the mechanism of herpesvirus integration and reactivation and will provide new tools for therapeutic excision of virus genomes from living cells.

 Publications

year authors and title journal last update
List of publications.
2017 Ahmed Kheimar, Renato Previdelli, Darren Wight, Benedikt Kaufer
Telomeres and Telomerase: Role in Marek’s Disease Virus Pathogenesis, Integration and Tumorigenesis
published pages: 173, ISSN: 1999-4915, DOI: 10.3390/v9070173
Viruses 9/7 2019-10-29
2017 Sonja Haertle, Ibrahim Alzuheir, Florian Busalt, Victoria Waters, Pete Kaiser, Benedikt B. Kaufer
Identification of the Receptor and Cellular Ortholog of the Marek\'s Disease Virus (MDV) CXC Chemokine
published pages: , ISSN: 1664-302X, DOI: 10.3389/fmicb.2017.02543
Frontiers in Microbiology 8 2019-10-29
2018 Darren Wight, Nina Wallaschek, Anirban Sanyal, Sandra Weller, Louis Flamand, Benedikt Kaufer
Viral Proteins U41 and U70 of Human Herpesvirus 6A Are Dispensable for Telomere Integration
published pages: 656, ISSN: 1999-4915, DOI: 10.3390/v10110656
Viruses 10/11 2019-10-29
2018 Anirban Sanyal, Nina Wallaschek, Mandy Glass, Louis Flamand, Darren Wight, Benedikt Kaufer
The ND10 Complex Represses Lytic Human Herpesvirus 6A Replication and Promotes Silencing of the Viral Genome
published pages: 401, ISSN: 1999-4915, DOI: 10.3390/v10080401
Viruses 10/8 2019-06-19
2016 Nina Wallaschek, Anirban Sanyal, Fabian Pirzer, Annie Gravel, Yasuko Mori, Louis Flamand, Benedikt B. Kaufer
The Telomeric Repeats of Human Herpesvirus 6A (HHV-6A) Are Required for Efficient Virus Integration
published pages: e1005666, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1005666
PLOS Pathogens 12/5 2019-06-19
2016 Nina Wallaschek, Annie Gravel, Louis Flamand, Benedikt B. Kaufer
The putative U94 integrase is dispensable for human herpesvirus 6 (HHV-6) chromosomal integration
published pages: 1899-1903, ISSN: 0022-1317, DOI: 10.1099/jgv.0.000502
Journal of General Virology 97/8 2019-06-19

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