Dendritic cells (DC) are crucial components of the early events of HIV infection. DC capture and internalize HIV-1 at mucosal surfaces and efficiently transfer, in the absence of viral replication in DC, the virus to CD4+ T cells through infectious synapses (trans-infection pathway). Alternatively, HIV-1 replicates in DC, the resulting DC-T cell viral transfer resulting exclusively from de novo produced viral particles in infected DC (cis-infection pathway). Our results clearly indicate that, for both pathways, HIV-1 is internalized into a novel, non-lysosomial, tetraspanin-rich compartment in DC. Subsequently, the differential recruitment, during the cis-infection pathway, of the AP-3 complex (adaptor protein complex 3), a complex involved in the viral protein Gag targeting to the membranes of late endosomes/MVBs, argues in favour of a potential role of the tetraspanin-rich compartment in HIV-1 production in DC.