Most likely, infection of CNS cells occurs as a result of transmigration of infected CD4 T cells and, possibly, macrophages across the blood-brain-barrier (BBB; Spudich and González-Scarano, 2012; Liu et al., 2000), a process that may be facilitated by the increased permeability of the BBB during the initial, highly replicative stage of HIV-1 infection. Here, CD4 is linked to HIV-1 infection.