Finally, the second and most studied mode of HIV-1 cell-to-cell infection of macrophages is related to the new mechanism we have documented that leads to rapid and massive virus transfer from infected CD4+ T cells to myeloid cells, including macrophages and also DCs and bone OCs, by a two-step viral envelope-dependent cell–cell fusion mechanism (Figure 3E) [57,58,89,90,132,136]. This evidence concerns the gene CD4 and infection.