Grant: Project Grant

Several studies have shown that early or pre-exposure treatments help prevent HIV-1 infection and the consequent destruction of the immune system which is then able to regain some control over the infection. In link with these observations, identification of new targets for HIV-1 involved in the first stages of infection remains the best option to eradicate HIV-1 infection. Dendritic cells (DCs) are the first immune cells which recognize HIV-1 in mucosal tissue. The initial interaction between HIV-1 and DCs occurs through attachment factors and we have identified the dendritic cell immunoreceptor (DCIR) as a key receptor. The binding of HIV-1 to DCIR allows the virus to be internalized, to escape the mounting of an immune response and to be transported to the lymphoid organs, where it gains entry into CD4 expressing T cells (CD4TL) by cell-to-cell transmission from DCs. Subsequent virus replication causes severe and irreversible depletion of CD4TL, bereaving the infected person of an efficient immune response against HIV-1. We are now interested in a possible role of DCIR in the early step of infection that appear to interfere with and ultimately compromise the immune response to HIV-1. We propose to test this hypothesis in vitro and in vivo using well-characterized cell models and humanized mouse models. We hope this novel approach will constitute a springboard for the development of new innovative therapeutic strategies against HIV-1 by blocking HIV-1 binding to DCs via DCIR without affecting the specific immune responses.