Although several groups have reported that HIV-1 latency may be a consequence of the direct infection of resting CD4+ T-cell subsets [14–16], particularly non-dividing follicular T helper cells in lymphoid tissues [17], overwhelming evidence, primarily derived from in vitro-engineered primary cell infection models, has bolstered the hypothesis that the establishment of latent HIV-1 reservoirs is a by-product of the achievement of immunological memory (reviewed in [18, 19]). The gene discussed is CD4; the disease is infection.