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Interactions du VIH-1 avec ses cellules cibles : recherche de nouveaux réservoirs et analyse du contrôle de la latence

Abstract : The identification of HIV cellular reservoirs and the understanding of the molecular mechanisms involved in the maintenance and reactivation of HIV latency are crucial to elaborate an efficient strategy to eliminate HIV from the body. My thesis project focused, on one hand, on the susceptibility of adipose tissue to HIV infection and its potential role as a new target tissue, and on the other hand, on the search for cellular candidates genes involved in the control of HIV latency.
Firstly, we would like to determine whether the low viral production observed after infection of human adipose cells with HIV was due to low infection or replication efficiency. We showed that infection with viral particles pseudotyped with X4 and R5 envelope is restricted due to insufficient viral receptor co-expression levels in preadipocytes. These results suggested that adipose tissue is not a preferential target for HIV in vivo and could not be considered as a new reservoir for the virus.
Secondly, we analysed differential gene expression on two HIV latently infected cell lines stimulated or not for the reactivation of latency by an histone deacetylase inhibitor. Analysis of microarrays data led us to select two candidate genes: NCoA3 and IRF8. We confirmed their differential expression at the transcriptional and translational levels and we analysed their functional role on HIV transcription. These results led us to postulate that NCoA3 and IRF8 could be involved respectively in the reactivation and maintenance of HIV latency.
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Submitted on : Thursday, March 13, 2008 - 2:27:25 PM
Last modification on : Monday, October 19, 2020 - 11:11:59 AM
Long-term archiving on: : Friday, September 28, 2012 - 11:10:23 AM


  • HAL Id : tel-00263880, version 1


Sandie Munier. Interactions du VIH-1 avec ses cellules cibles : recherche de nouveaux réservoirs et analyse du contrôle de la latence. Biochimie [q-bio.BM]. Université Paris-Diderot - Paris VII, 2005. Français. ⟨tel-00263880⟩



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