Downmodulation of CCR7 by HIV-1 Vpu Results in Impaired Migration and Chemotactic Signaling within CD4(+) T Cells

作者：Ramirez Peter W; Famiglietti Marylinda; Sowrirajan Bharatwaj; DePaula Silva Ana Beatriz; Rodesch Christopher; Barker Edward; Bosque Alberto; Planelles Vicente^*

来源：Cell Reports, 2014, 7(6): 2019-2030.

DOI：10.1016/j.celrep.2014.05.015

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 Ca2+, 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.

• 出版日期2014-6-26