TYMSTR, a putative chemokine receptor selectively expressed in activated T cells, exhibits HIV-1 coreceptor function
TYMSTR, a putative chemokine receptor selectively expressed in activated T cells, exhibits HIV-1 coreceptor function
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DOI：
10.1016/s0960-9822(06)00292-2
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发表时间：
1997-09-01
期刊：
影响因子：
9.2
通讯作者：
Moser, B
中科院分区：
文献类型：
--
作者：
Loetscher, M;Amara, A;Moser, B
背景资料：趋化因子与特异性受体结合并介导白细胞向炎症部位迁移。最近，一些趋化因子受体，特别是CXCR 4和CCR 5，已被证明是人类免疫缺陷病毒（HIV）感染的靶细胞上的必需融合因子;与这些受体结合的趋化因子也显示出作为HIV感染的有效抑制剂。在此，我们描述了一种新的，结果：我们分离了一种人趋化因子受体的cDNA，我们将其命名为TYMSTR（T淋巴细胞表达的七跨膜结构域受体）。TYMSTR基因定位于人3号染色体，编码一种与趋化因子受体具有高度同一性的蛋白。TYMSTR mRNA在白细胞介素-2刺激的T淋巴细胞中选择性表达，而在新鲜分离的淋巴细胞和白细胞或相关细胞系中不表达。在32种人趋化因子和其他潜在配体中鉴定了TYMSTR的天然配体。共表达TYMSTR和人CD 4的细胞与表达嗜巨噬细胞（M）的HIV-1和嗜T细胞系（T）的HIV-1分离株的包膜糖蛋白的细胞融合，此外，感染性，T-嗜性HIV-I颗粒TYMSTR/CD 4表达细胞导致病毒进入和前病毒DNA formation.Conclusions：我们的研究结果表明，TYMSTR，与CD 4相结合，介导HIV-I融合和进入。TYMSTR在CD 4（+）T淋巴细胞中的高水平表达及其对T嗜性和M嗜性HIV-1毒株的选择性，提示TYMSTR可能在HIV感染的早期和晚期起辅助受体的作用。
Background: Chemokines bind to specific receptors and mediate leukocyte migration to sites of inflammation, Recently, some chemokine receptors, notably CXCR4 and CCR5, have been shown to be essential fusion factors on target cells for infection by human immunodeficiency virus (HIV); the chemokines bound by these receptors have also been shown to act as potent inhibitors of HIV infection, Here, we describe the isolation of a novel, putative chemokine receptor,Results: We have isolated the cDNA for a putative human chemokine receptor, which we have termed TYMSTR (T-lymphocyte-expressed seven-transmembrane domain receptor), The TYMSTR gene is localized to human chromosome 3 and encodes a protein thai has a high level of identity with chemokine receptors. TYMSTR mRNA was selectively expressed in interleukin-2-stimulated T lymphocytes but not in freshly isolated lymphocytes and leukocytes or related cell lines, The natural ligand for TYMSTR was Rot identified among 32 human chemokines and other potential ligands, Cells coexpressing TYMSTR and human CD4 fused with cells expressing envelope glycoproteins of macrophage (M)-tropic HIV-1 as well as T-cell line (T)-tropic HIV-1 isolates, Addition of infectious, T-tropic HIV-I particles to TYMSTR/CD4-expressing cells resulted in viral entry and proviral DNA formation.Conclusions: Our findings demonstrate that TYMSTR, in combination with CD4, mediates HIV-I fusion and entry. The high-level expression of TYMSTR in CD4(+) T lymphocytes and the selectivity of this receptor for T-tropic and M-tropic HIV-1 strains indicates that TYMSTR might function as HIV coreceptor at both early and late stages of infection.