HIV can exploit a preexisting exosome trans-dissemination pathway intrinsic to mature DCs, allowing the final trans-infection of CD4⁺ T cells. (A) Exosomes can transfer antigens from infected, tumoral, or antigen-presenting cells to mDCs, increasing the number of DCs bearing a particular antigen and amplifying the initiation of primary adaptive immune responses through the MHC II pathway, cross-presentation, or the release of intact exosomes, a mechanism described here as trans-dissemination. (B) HIV gains access into mDCs by hijacking this exosome trans-dissemination pathway, thus allowing for the final trans-infection of CD4⁺ T cells.