The latent HIV-1 reservoir mainly resides in resting memory CD4+ T cells (Chun et al., 1997; Finzi et al., 1997; Chomont et al., 2009), but they are normally not the direct targets for infection, due to the blocks in reverse transcription (Korin and Zack, 1998), integration (Bukrinsky et al., 1992) and host restriction by SAMHD1 (Baldauf et al., 2012). Here, SAMHD1 is linked to infection.