Cell Reports · 2014 · 67 citations · 57 references
Life SciencesImmunologyMolecular BiologyCell SignalingMolecular VirologySignal TransductionChemokine SignalingImmune Cell SignalingImmune Cell TraffickingLeukocyte TraffickingLymphocyte TraffickingT Cell BiologyCd4 Positive T CellsCentral Memory T CellsChemotactic Cell RecruitmentChemotactic MediatorsChemotactic SignalingNaive T CellsTrans-golgi TransportTransmembrane Proteins
The chemokine receptor CCR7 plays a crucial role in the homing of central memory and naive T cells to peripheral lymphoid organs. Here, we show that the HIV-1 accessory protein Vpu downregulates CCR7 on the surface of CD4(+) T cells. Vpu and CCR7 were found to specifically interact and colocalize within the trans-Golgi network, where CCR7 is retained. Downmodulation of CCR7 did not involve degradation or endocytosis and was strictly dependent on Vpu expression. Stimulation of HIV-1-infected primary CD4(+) T cells with the CCR7 ligand CCL19 resulted in reduced mobilization of Ca(2+), reduced phosphorylation of Erk1/2, and impaired migration toward CCL19. Specific amino acid residues within the transmembrane domain of Vpu that were previously shown to be critical for BST-2 downmodulation (A14, A18, and W22) were also necessary for CCR7 downregulation. These results suggest that BST-2 and CCR7 may be downregulated via similar mechanisms.
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