With the right combination of virus and host macaque species, many of the key features of HIV-1 infection in humans can be recapitulated in these models, including predominant infection of CD4+ T cells [5,6,7], early destruction of CD4+ T cells in gut mucosal sites [7,8,9], the development of chronic immune activation and inflammation [10,11,12,13], the establishment of a persistent rebound-competent viral reservoir [14,15,16], and the gradual depletion of CD4+ T cells in blood and progression to acquired immunodeficiency syndrome (AIDS) [17,18]. The gene discussed is CD4; the disease is HIV-1 infection.