Date : 6/2/2010
Mucosal entry of HIV an mucosal immunology U1016 CNRS UMR 8104
22 rue Mechain 75014 paris
Director : Miorgane Bmsel
phone : +33 140516497
Subjects / Tools-Methodologies
1 : HIV/eplants/reconstruction of mucosa
2 : mucosa/confocal and live fluorescent microscopy
3 : mucosal immunity/cell biology and cellular immunology
Summary of lab's interests
Mucosal entry of HIV an mucosal immunity The lab studies the initial steps of HIV entry at various mucosal site using primary viruses cells and primary humman mucosal cells, and human genital fluids.. Systems have been established. We also study the mucosal humoral immune response induced by HIV infection , but also that one that confer protecion to highly exposed individual that remain seronegative despite unprotected sexual intercourse with HIV seropositive partners. Finaly, in collaboration with both academic and private partners, we translated our fondamental findings into mucosal vaccines. We evaluate vaccine efficacy by vaccination in the monkey model following virulent mucosal challenge. With these models, we try to correlate protection to an adapted mucosal humoral response as well as to the innate immune response.
Summary of project
The Foreskin has been demonstrated to be an important genital portal of entry for HIV-1 following randomized circumcision assays. It could efficiently decrease HIV-1 sexual acquisition by the male upon heterosexual intercourse. However, mechanisms of viral entry at the foreskin remain unclear. Based on host laboratory results, it was shown that within 1hr post inoculation, the inner surface foreskin is more susceptible than the outer foreskin to HIV-1, after interaction of HIV+ cells with the tissues. In this project, the student will investigate the mechanisms of HIV-1 entry at the foreskin at longer time points (from 4 to 48hr) where a crosstalk could occur between the innate T cells, antigen presenting cells, and the epithelial cells, modulated by the molecules secreted from the tissues. The student will first question the mechanisms of viral synapse formation between the HIV+ cells and mucosal surface for efficacious transmission. Then, the exact role of LC in HIV-1 entry should be elucidated. Simultaneously, the potential role of the epithelium-localized immune cells acting against HIV-1 will be investigated. Ultimately, the student will study the potential functions of molecules secreted from the tissues challenged with HIV-1. To achieve our goals, the student will use a tissue explant model maintaining its integrity up to 48hr. It will be inoculated with HIV+ cells infected either by primary HIV-1 strain or recombinant strain in parallel with an envelope incorporation deficient virus. Several techniques, such as: microscopy (confocal and live fluorescence microscopy in P3 confinement conditions), flow cytometry, microarrays, biochemistry, also traditional cytology, immunology and genetic methods will be applied for analysis. A highly regulated crosstalk is maintained in the normal foreskin epithelium. In contrast, HIV-1 entry at the foreskin triggers specific signals that disrupt the immune homeostasis facilitating its transmission.