a, Activation of naive CD4+ T cells renders the cells highly susceptible to infection with simian immunodeficiency virus (SIV), which becomes integrated into the host-cell genome to allow viral replication. Most CD4+ T cells die rapidly after infection, but a small fraction survives and reverts back to a resting memory state, in which SIV gene expression is turned off, resulting in a latent reservoir of the virus. Subsequent activation of these cells can restart virus production. b, Antiretroviral therapy (ART) soon after infection can stop more cells from becoming infected, but does not affect the fate of already infected cells, and some survive to seed the latent reservoir. Whitney et al.6 show that a viral reservoir is established within days of SIV infection. c, In vaccinated animals, SIV-specific cytotoxic T cells that are generated in response to the vaccine can kill infected cells before they revert back to the resting state, thereby preventing the establishment of a latent reservoir.