The HIV-1 Gp120/CXCR4 axis promotes CCR7 ligand-dependent CD4 T cell migration: CCR7 homo- and CCR7/CXCR4 hetero-oligomer formation as a possible mechanism for up-regulation of functional CCR7.
The HIV-1 Gp120/CXCR4 axis promotes CCR7 ligand-dependent CD4 T cell migration: CCR7 homo- and CCR7/CXCR4 hetero-oligomer formation as a possible mechanism for up-regulation of functional CCR7.
复制标题
DOI：
10.1371/journal.pone.0117454
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Miyasaka M
中科院分区：
文献类型：
--
作者：
Hayasaka H;Kobayashi D;Yoshimura H;Nakayama EE;Shioda T;Miyasaka M
在人类免疫缺陷病毒（HIV）感染期间，感染细胞向淋巴结的迁移增强导致HIV-1的有效繁殖。选择性趋化因子受体，包括CXCR 4和CCR 7，可能在这一过程中发挥作用，但调节趋化因子依赖性T细胞迁移的病毒因子仍然相对不清楚。CXCR 4配体趋化因子CXCL 12与CCR 7配体趋化因子CCL 19和CCL 21之间的功能性合作增强了体外CCR 7依赖性T细胞运动性以及体内细胞运输到淋巴结中。在这项研究中，我们报告了一种重组形式的病毒CXCR 4配体，X4-tropic HIV-1 gp 120，增强了CD 4 T细胞对CCR 7配体的反应，这种反应依赖于CXCR 4和CD 4，并且这种作用被HIV-1病毒体重现。在体内转移实验中，HIV-1 gp 120显著增强了CCR 7依赖性CD 4 T细胞从小鼠足垫向引流淋巴结的迁移。我们还证明了CXCR 4表达是CCR 7在CD 4 T细胞表面上稳定表达所必需的，而CXCR 4信号转导促进CCR 7配体与细胞表面的结合并增加CCR 7同源寡聚体以及CXCR 4/CCR 7异源寡聚体的水平而不影响CCR 7表达水平。我们的研究结果表明，HIV诱导的CXCR 4信号通过上调CCR 7功能促进CCR 7依赖性CD 4 T细胞迁移，这可能是由CD 4 T细胞表面CCR 7同源寡聚体和CXCR 4/CCR 7异源寡聚体的形成增加诱导的。
During human immunodeficiency virus (HIV) infection, enhanced migration of infected cells to lymph nodes leads to efficient propagation of HIV-1. The selective chemokine receptors, including CXCR4 and CCR7, may play a role in this process, yet the viral factors regulating chemokine-dependent T cell migration remain relatively unclear. The functional cooperation between the CXCR4 ligand chemokine CXCL12 and the CCR7 ligand chemokines CCL19 and CCL21 enhances CCR7-dependent T cell motility in vitro as well as cell trafficking into the lymph nodes in vivo. In this study, we report that a recombinant form of a viral CXCR4 ligand, X4-tropic HIV-1 gp120, enhanced the CD4 T cell response to CCR7 ligands in a manner dependent on CXCR4 and CD4, and that this effect was recapitulated by HIV-1 virions. HIV-1 gp120 significantly enhanced CCR7-dependent CD4 T cell migration from the footpad of mice to the draining lymph nodes in in vivo transfer experiments. We also demonstrated that CXCR4 expression is required for stable CCR7 expression on the CD4 T cell surface, whereas CXCR4 signaling facilitated CCR7 ligand binding to the cell surface and increased the level of CCR7 homo- as well as CXCR4/CCR7 hetero-oligomers without affecting CCR7 expression levels. Our findings indicate that HIV-evoked CXCR4 signaling promotes CCR7-dependent CD4 T cell migration by up-regulating CCR7 function, which is likely to be induced by increased formation of CCR7 homo- and CXCR4/CCR7 hetero-oligomers on the surface of CD4 T cells.
登录
查看更多内容
影响因子：
5.5
作者：
Lee, C;Liu, QH;Collman, RG
通讯作者：
Collman, RG
影响因子：
5.4
作者：
Bandres, JC;Wang, QF;Gorny, MK
通讯作者：
Gorny, MK
影响因子：
56.9
作者：
Lapham, CK;Ouyang, J;Golding, H
通讯作者：
Golding, H
DOI：
10.1073/pnas.0804286105
发表时间：
2008-07-22
影响因子：
11.1
作者：
Contento, Rita Lucia;Molon, Barbara;Viola, Antonella
通讯作者：
Viola, Antonella
影响因子：
5.4
作者：
Green, Daniel S.;Center, David M.;Cruikshank, William W.
通讯作者：
Cruikshank, William W.