التفاصيل البيبلوغرافية
العنوان: |
Downmodulation of CCR7 by HIV-1 Vpu Results in Impaired Migration and Chemotactic Signaling within CD4+ T Cells. |
المؤلفون: |
Ramirez, Peter W., Famiglietti, Marylinda, Sowrirajan, Bharatwaj, DePaula-Silva, Ana Beatriz, Rodesch, Christopher, Barker, Edward, Bosque, Alberto, Planelles, Vicente |
المصدر: |
Cell Reports; Jun2014, Vol. 7 Issue 6, p2019-2030, 12p |
مستخلص: |
Summary: 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. [Copyright &y& Elsevier] |
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قاعدة البيانات: |
Complementary Index |