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Challenging the hidden HIV: understanding the block on transcriptional reactivation to eradicate infection

Challenging the hidden HIV: understanding the block on transcriptional reactivation to eradicate infection

Objective

Highly active antiretroviral therapy (HAART) has profoundly decreased morbidity and mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Nonetheless, HIV-1 has not been eradicated by HAART. Factors affecting HIV-1 latency presen t formidable obstacles for therapeutic intervention and the need for novel therapeutic strategies specifically targeting HIV-1 latency has become evident. However, therapeutic targeting of HIV-1 latency requires an understanding of the basic mechanisms r egulating viral quiescence and activation. Exploring the scientific possibilities of new therapies targeting HIV-1 latency may hold new promise of eventual HIV-1 eradication. The proposal aims at identifying the key cellular and viral factors that control HIV latency and reactivation. Cellular factors that affect HIV-1 latency could be proteins controlling chromatin silencing and transcriptional reactivation through interaction with viral proteins, as well as small interfering RNAs produced naturally in t he infected cells that control silencing. Furthermore, we intend to explore the possibility that HIV-1 itself could modulate the cellular siRNA machinery to control its own expression. In order to approach these topics a wide array of techniques will be implemented. A Proteomic approach will be used to identify cellular factors involved in the control of viral latency and reactivation. The recruitment of these factors to the integrated viral promoter will be monitored by chromatin immunoprecipitation a nd by highly innovative fluorescent optical tools. Finally, the information gained from these basic studies will be exploited to design specific siRNA targeted to viral latency.

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

Address

Rue Michel Ange 3
Paris

France

Administrative Contact

Monsef BENKIRANE (Dr)

Participants (4)

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INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY

Italy

ACADEMISCH ZIEKENHUIS BIJ DE UNIVERSITEIT VAN AMSTERDAM

Netherlands

UNIVERSITY OF AARHUS

Denmark

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

Project information

Grant agreement ID: 12182

  • Start date

    1 January 2005

  • End date

    31 December 2007

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 982 999

  • EU contribution

    € 657 998

Coordinated by:

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

France