In vivo, HIV infection results in the progressive depletion of CD4+ T cells, leading to a state of profound immunodeficiency known as acquired immunodeficiency syndrome (AIDS) with the emergence of opportunistic infections and peculiar types of cancer resulting in the death of >95% of infected individuals if combination antiretroviral therapy (cART) is not administered; conversely, HIV infection of tissue macrophages neither causes their depletion in vitro nor in vivo, perhaps reflecting the coevolution between lentiviruses and myeloid cells [2,3]. The gene discussed is CD4; the disease is AIDS.