Fig. 3 Role of distinct macrophage populations on development of HIV-1 pathogenesis. Despite being ontogenically distinct, YSDMs and MDMs have a critical role in the maintenance of viral replication, reflected in the development of chronic HIV-1 pathogenesis. MDMs are derived from the terminal differentiation of myeloid bone marrow progenitor cells and several studies have demonstrated that MDMs obtained from HIV-1 patients have functional impairments  in vitro. 12 ,  13 ,  14  Although monocytes are poorly infected in the bloodstream, HIV-1 can infect directly CD34+ progenitor cells and induce functional impairments during hematopoiesis. 29 ,  30 ,  31  Some tissue macrophages are derived from monocyte differentiation of peripheral tissues or from Yolk Sac progenitors seeded during the early steps of embryogenesis. 17 ,  18 ,  19  Both of these subsets can be chronically infected and cause the spread of virus to other cells. In parallel, microglia and other CNS (as perivascular and meningeal) macrophages are directly derived from YS progenitors and contribute to development of neuronal death and HAND found mainly on untreated HIV patients. 24 ,  33