After reaching the PM, like those of other lentiviruses, HIV-1 Env undergoes rapid endocytosis, which is mediated by the interaction between the μ2 subunit of the clathrin adaptor AP-2 and a membrane-proximal, Tyr-based motif (YxxL) in the gp41 CT [58, 61, 62]. Although some of the endocytosed Env is recycled back to the PM, most retroviral Env is associated with intracellular membranes [63, 64] . The level of gp120-gp41 oligomers on HIV-1 virions is relatively low [33] . Maintaining low levels of Env at the cell surface allows the infected cells to evade the host immune response and to avoid induction of Env-mediated apoptosis. Gammaretroviruses such as MLV and MPMV also have dileucine-and Tyr-based motifs in their Env CT. These motifs are important to regulate intracellular trafficking of Env of both retroviruses via interactions with clathrin adaptors [65, 66].