Although strong evidence concerning the in vivo occurrence of HIV-1 trans-infection are lacking owing to the absence of optimal animal models and obvious difficulties to perform experiments (e.g., poor reconstitution of human myeloid compartment in humanized mouse models), ex vivo experiments revealed that endogenous myeloid DCs can trans-infect CD4+ T cells with HIV-1 (Shen et al., 2014; Reyes-Rodriguez et al., 2016; Trifonova et al., 2018). This evidence concerns the gene CD4 and infection.