Title:HIV-1 Vpu Interference with Innate Cell-mediated Immune Mechanisms
VOLUME: 10 ISSUE: 4
Author(s):Johan K. Sandberg, Sofia K. Andersson, Susanna M. Bachle, Douglas F. Nixon and Markus Moll
Affiliation:CIM, Department of Medicine, F59, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.
Keywords:HIV-1, iNKT cells, CD1d, Vpu, NK cells, immune evasion, NTB-A, Nef, Vpr, down-regulation
Abstract: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
