HIV-1 induces DCIR expression in CD4+ T cells

The c-type lectin receptor dcir,which has been shown very recently to act as an attachment factor for hiv-1 in dendritic cells,is expressed predominantly on antigen-presenting cells. however,this concept was recently challenged by the discovery that dcir can also be detected in cd4+ t cells found in the synovial tissue from rheumatoid arthritis (ra) patients. given that ra and hiv-1 infections share common features such as a chronic inflammatory condition and polyclonal immune hyperactivation status,we hypothesized that hiv-1 could promote dcir expression in cd4+ t cells. we report here that hiv-1 drives dcir expression in human primary cd4+ t cells isolated from patients (from both aviremic/treated and viremic/treatment naïve persons) and cells acutely infected in vitro (seen in both virus-infected and uninfected cells). soluble factors produced by virusinfected cells are responsible for the noticed dcir up-regulation on uninfected cells. infection studies with vpr- or nef-deleted viruses revealed that these two viral genes are not contributing to the mechanism of dcir induction that is seen following acute infection of cd4+ t cells with hiv-1. moreover,we report that dcir is linked to caspase-dependent (induced by a mitochondria-mediated generation of free radicals) and -independent intrinsic apoptotic pathways (involving the death effector aif). finally,we demonstrate that the higher surface expression of dcir in cd4+ t cells is accompanied by an enhancement of virus attachment/entry,replication and transfer. this study shows for the first time that hiv-1 induces dcir membrane expression in cd4+ t cells,a process that might promote virus dissemination throughout the infected organism. © 2010 lambert et al.