Our main interest is to understand the regulation of HIV-1 gene expression. Our projects aim to determine mechanisms of both activation and repression of viral transcription. This is a critical step of the HIV-1 life cycle since it controls virus production and viral post-integration latency. Indeed, HIV-1 infection is a dynamic process involving continuous rounds of infection, replication and cell death. Continuous viral replication causes the loss of CD4⁺ T cells and therefore determines the rate of progression to immunodeficiency in infected individuals.

The use of highly active anti-retroviral therapy (HAART) has recently raised the possibility of a cure for HIV-infected individuals. Despite this success, there have been reports of viral rebound after interruption of HAART in infected individuals in whom HIV plasma viremia was undetectable. The persistence of latently infected, resting CD4+ T cells, containing an integrated DNA provirus that is neither visible to the immune system, nor accessible to current anti-HIV therapies, seriously challenges the hope of complete viral eradication. This latent reservoir of HIV, in the pool of resting CD4+ T cells, is established rapidly in primary HIV infection and can persist for an extended period of time. Assuming that this reservoir is only 10⁵ cells per individual, it will take 10 to 60 years of HAART treatment (depending on the study) to totally eradicate the virus. Several combinations of activating stimuli induce HIV expression from this pool of latently infected cells. Viewed in this context, it is critical to define the molecular mechanisms involved in the establishment of latency and the reactivation of the viral expression.

Recent studies have clearly shown that chromatin is an integral component of HIV replication. The heterogeneous structure of cellular chromatin controls viral expression by directly regulating (i) integration site selection and (ii) transcriptional reactivation. Moreover, interaction between HIV-1 infection and the RNAi/miRNA pathway could result in the establishment and maintenance of HIV-1 latency.

In order to approach these topics a wide array of techniques are implemented. A Proteomic approach is used to identify cellular factors involved in the control of viral latency and reactivation. The recruitment of these factors to the integrated viral promoter is monitored by chromatin immunoprecipitation and by highly innovative fluorescent optical tools. 

We are mainly focusing on:

1) the involvement of chromatin modifiers in HIV-1 gene activation and repression (Associated Page).

2) Regulation of the viral transactivator Tat transcriptional activity by post translational modifications (Associated Page).

3) The involvement of proteasome in transcription (Associated Page).

4) The cross-talk between RNAi machinery and HIV-1 replication (Associated Page).