The HIV-1 pandemic continues to expand while no effective vaccine is yet available. Finding new therapeutic targets and drugs is therefore crucial. We have previously shown that the dendritic cell immunoreceptor (DCIR), a C-type lectin receptor expressed in dendritic cells (DCs), acts as an attachment factor for HIV-1 to DCs and contributes to HIV-1 transmission to CD4+ T lymphocytes (CD4TL). Directly involved in HIV-1 infection, DCIR is expressed in apoptotic or infected CD4TL and promotes trans-infection to bystander cells. The aim of the present study is to characterize the extracellular domain of DCIR and to test chemical inhibitors of HIV-1 attachment thereto.
We present the first three-dimensional model of DCIR structure. Based on this structure, several inhibitors were selected to target viral interaction with the carbohydrate recognition domain and the EPS motif. Preliminary screening using Raji-CD4-DCIR cells identified two inhibitors that decreased HIV-1 attachment and propagation. These inhibitors did not affect the proliferation of peripheral blood mononuclear cells.
The results of this study thus suggest structures for novel molecules capable of blocking HIV-1 transmission by DCs and CD4TL.