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Metzner Günthard

Fakultäten » Medizinische Fakultät » Infektionskrankheiten und Spitalhygiene, Klinik für » Prof. Dr. Huldrych Günthard » Metzner Günthard

Completed research project

Title / Titel HIV-1 integration sites and their impact on HIV-1 pathogenesis
PDF Abstract (PDF, 14 KB)
Summary / Zusammenfassung Retroviral integration into the genome of the host cell is a very important step in the life cycle of a retrovirus. The integration site decides about the fate of the provirus. Integration into transcription-supporting units increases the chance of pursuing the retroviral life cycle and to produce the next generation of viruses. Integration into more silenced parts of the genome has the advantage that the virus can hide and persist, thus, establishing a latent reservoir. For human beings, this is particularly relevant in the context of infection with human immunodeficiency virus type 1 (HIV-1). HIV-1 can not only replicate to high levels, but it also establishes a life-long infection by generating a latent reservoir. It is still not known how HIV-1 achieves the state of latency. We will study changes in the frequencies and patterns of HIV-1 integration sites separately in its main target cell subpopulations from HIV-1 infected individuals followed over at least 5 years after primary HIV-1 infection. And we will investigate systematically chromosomal features surrounding HIV-1 integration sites and their influence on HIV-1 transcription by using a novel HIV-1 LTR-based reporter construct that will enable us to differentiate between (1) activated, (2) resting and inducible, (3) resting and non-inducible, and (4) silenced cells. These studies will help us understand how HIV-1 establishes and maintains a latent reservoir and which impact HIV-1 integration sites have on the pathogenesis of HIV-1. And it will enable us to obtain detailed insights into the regulation of HIV-1 transcription, thus, opening ways for novel therapeutic approaches to eradicate HIV-1.
Project leadership and contacts /
Projektleitung und Kontakte
Prof. Dr. Karin Metzner, MD (Project Leader) karin.metzner@usz.ch
Prof. Dr. Huldrych Günthard, MD (Project Leader) huldrych.guenthard@usz.ch
Funding source(s) /
Unterstützt durch
SNF (Personen- und Projektförderung)
 
Duration of Project / Projektdauer Apr 2012 to Jun 2016