HIV Nef, MLV glycoGag, and EIAV S2 antagonize TIM-mediated inhibition of HIV release, which is potentiated by SERINC. HIV Nef promotes the internalization of TIM-1, resulting in its decreased expression on the cell surface. Nef also sequesters TIM-1 into an autophagy-related, non-degradative compartment, which prevents TIM-1 trafficking to the plasma membrane. SERINC proteins (SERINC3 and SERINC5) can stabilize the expression of TIM-1 in viral producer cells, thus potentiating its inhibitory effect on viral release; both SERINCs and TIMs are counteracted by Nef, glycoGag, and S2, resulting in increased viral release.