HIV-1 Vpu Promotes Release and Prevents Endocytosis of Nascent Retrovirus Particles from the Plasma Membrane
Figure 12
Model for the Role of Vpu in Retroviral Particle Release
Retroviral Gag molecules targeted to the PM (by unknown mechanisms) require the recruitment of class E VPS factors to enable budding of mature virions. At this point, nascent viral particles are subject to an unknown, subtilisin-sensitive, host-cell type-specific restriction (depicted as a question mark) that results in their retention at the cell surface. Subsequently, endocytosis by a dynamin-, EPS-15-, and Rab5a-dependent process result in intracellular accumulation in early/late endosomes, where they may be simply sequestered, or perhaps destroyed, in lysosomes. Vpu overcomes this restriction, leading to more efficient release of virions from the cell surface. In contrast, inhibition of endocytosis by DN mutants of dynamin, EPS-15, or Rab5a prevents the accumulation of virions in endosomes, but does not enhance virion release, suggesting Vpu inhibits a specific host-restriction activity, rather than imposing a generalized inhibition on endocytosis.
doi: https://doi.org/10.1371/journal.ppat.0020039.g012