Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes
Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes
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DOI：
10.1182/blood-2004-07-2850
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发表时间：
2005-08-01
期刊：
影响因子：
20.3
通讯作者：
Bangham, CRM
中科院分区：
文献类型：
--
作者：
Barnard, AL;Igakura, T;Bangham, CRM
细胞间的接触是人类嗜T淋巴细胞病毒1型(HTLV-1)有效传播所必需的。感染HTLV-1的细胞将其微管组织中心(MTOC)极化到细胞-细胞连接处；HTLV-1核心(GAG)复合体和HTLV-1基因组在接触点积累，然后转移到未感染的细胞。然而，HTLV-1复合体这种细胞骨架极化和转运的机制尚不清楚。在这里，我们测试了一个假设，即特定的T细胞表面配体的结合与HTLV-1感染在导致MTOC到细胞接触区的极化方面是协同的。我们发现，抗细胞间黏附分子-1(ICAM-1；CD54)的抗体在HTLV-1感染的细胞中以更高的频率引起MTDC极化。在感染HTLV-1的细胞上，CaM-1表达上调，细胞表面的ICAM-1上调HTLV-1基因表达。我们认为，ICAM-1和HTLV-1 Tax蛋白之间的正反馈环促进了病毒学突触的形成，并有助于HTLV-1的T细胞趋向性。相反，抗CD3或bD28抗体诱导的T细胞MTOC极化被HTLV-1感染显著抑制。
Cell-cell contact is required for efficient transmission of human T-lymphotropic virus type 1 (HTLV-1). An HTLV-1-infected cell polarizes its microtubule-organizing center (MTOC) toward the cell-cell junction; HTLV-1 core (Gag) complexes and the HTLV-1 genome accumulate at the point of contact and are then transferred to the uninfected cell. However, the mechanisms involved in this cytoskeletal polarization and transport of HTLV-1 complexes are unknown. Here, we tested the hypothesis that engagement of a specific T-cell surface ligand is synergistic with HTLV-1 infection in causing polarization of the MTOC to the cell contact region. We show that antibodies to intercellular adhesion molecule-1 (ICAM-1; CD54) caused MTDC polarization at a higher frequency in HTLV-1-infected cells. CAM-1 is upregulated on HTLV-1-infected cells, and, in turn, ICAM-1 on the cell surface upregulates HTLV-1 gene expression. We propose that a positive feedback loop involving ICAM-1 and HTLV-1 Tax protein facilitates the formation of the virologic synapse and contributes to the T-cell tropism of HTLV-1. In contrast, MTOC polarization induced in T cells by antibodies to CD3 or bD28 was significantly inhibited by HTLV-1 infection.