Figure 2.

Multiple modes of Vpu-mediated bone marrow stromal cell antigen 2 (BST2) counteraction. Under normal conditions, de novo BST2 protein is supplied to the plasma membrane (PM) through the secretory system. Constitutive recycling of BST2 occurs from the PM to endosomes, as well as between endosomes and the trans-Golgi network (TGN) (right). During HIV-1 infection in the absence of Vpu, accumulation of BST2 at sites of viral assembly at the cell surface results in the incorporation of BST2 molecules into nascent virions, leading to inhibition of virus particle release. In select systems, these BST2-entrapped virions may be internalized and potentially degraded. During infection with Vpu-competent HIV-1, Vpu intercepts and binds BST2 within the vesicular system, resulting in their sequestration in endosomal structures in an AP-1 and clathrin-dependent manner (left). In the context of group M Vpu variants, sequestered BST2 proceeds to subsequent lysosomal degradation along the endosomal sorting complexes required for transport (ESCRT) pathway. Vpu can also bind BST2 at the cell membrane to induce its removal from sites of virus assembly using an AP-2 and clathrin-dependent system. This pool of BST2 may subsequently recycle into endosomal compartments for sequestration and degradation.