HIV-1 Vpu Interference with Innate Cell-mediated Immune Mechanisms

The HIV-1 accessory protein Vpu is emerging as a viral factor with a range of activities devoted to counteracting host innate immunity. Here, we review recent findings concerning the role of Vpu in hampering activation of cellular immune responses mediated by CD1d-restricted invariant natural killer T (iNKT) cells and natural killer (NK) cells. The two key findings are that Vpu interferes with CD1d expression and antigen presentation, and also with expression of the NK cell activation ligand NK-T and B cell antigen (NTB-A). Both these activities are mechanistically distinct from CD4 and Tetherin (BST-2) down-modulation. We summarize the mechanistic insights gained into Vpu interference with CD1d and NTB-A, as well as important challenges going forward, and discuss these mechanisms in the context of the role that iNKT and NK cells play in HIV-1 immunity and immunopathogenesis.