To progress in the basic knowledge of host cell/HIV genome relationship in order to better adapt future antiviral therapies to the strategies of latency, reactivation and replication used by HIV to persist in immunocompetent cells and suppress their functions.
Five teams from France, United Kingdom and Spain imbricate their efforts to characterise molecules targetable for antiviral intervention, on the base of their participation in the transduction and transcription pathways controlling the expression of integrated HIV provirus in immunocompetent cells that are natural targets of HIV infection, namely CD4 T lymphocytes and macrophages. The project focuses on the following aspects :
- Characterisation of the IkappaB kinase and/or phosphatase directly controlling the phosphorylation, ubiquitinylation and degradation of IkappaB resulting in activation of NF-kappaB.
- The regulation of nuclear import and export of NF-kappaB and IkappaB, and the mechanism of termination of NF-kappaB function by nuclear translocation of IkappaB.
- The role of interactions between NF-kappaB and IkappaBalpha in the control of HIV genome transcription in transformed and normal T cells and macrophages.
- The influence of HIV particles, whether infectious or not, on the above events and on the regulation of transduction pathways controlling T lymphocyte activation and viability.
- The effects on the NF-kappaB system of non-toxic compounds capable of dissociating NF-kappaB translocation and activity, and suppressing HIV replication.