Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 use different receptor complexes to enter T cells
Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 use different receptor complexes to enter T cells
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DOI：
10.1128/jvi.00389-06
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发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Ruscetti, Francis W.
中科院分区：
文献类型：
--
作者：
Jones, Kathryn S.;Fugo, Kazunori;Ruscetti, Francis W.
使用贴壁细胞系的研究表明，葡萄糖转运蛋白-1(GLUT-1)可以作为人类T细胞白血病病毒1型(HTLV)的受体。在原代CD4(+)T细胞中，需要硫酸乙酰肝素蛋白多糖(HSPGs)才能有效进入HTLV-1。在这里，我们研究了HSPGs和GLUT-1在HTLV-1和HTLV-2 Env介导的结合和进入原代T细胞中的作用。对活化的原代T细胞表面的检测显示，作为HTLV-1的主要靶点的CD4(+)T细胞表达的HSPGs水平明显高于CD8(+)T细胞。相反，作为HTLV-2的主要靶点的CD8(+)T细胞表达GLUT-1的水平明显高于CD4(+)T细胞。在此条件下，CD8(+)T细胞的HTLV-2表面糖蛋白(SU)结合率和病毒侵入率明显高于CD8(+)T细胞，而CD4(+)T细胞的HTLV-1表面糖蛋白(SU)结合率和病毒侵入率明显高于CD8(+)T细胞。与HTLV-1/HTLV-2SU重组体的结合研究表明，优先与表达高水平HSPG的CD4‘T细胞结合在SU的C末端部分。转染研究表明，在CD4(+)T细胞中过表达GLUT-1增加了HTLV-2的进入，而在CD8(+)T细胞上表达HSPGs则增加了HTLV-1的进入。这些研究表明，HTLV-1和HTLV-2对T细胞进入的要求不同，提示这两种病毒在体外转化的细胞嗜性和体内病理生物学上的差异反映了它们在参与进入的CD4‘和CD8(+)T细胞上的不同包膜蛋白和分子之间的相互作用。
Studies using adherent cell lines have shown that glucose transporter-1 (GLUT-1) can function as a receptor for human T-cell leukemia virus type 1 (HTLV). In primary CD4(+) T cells, heparan sulfate proteoglycans (HSPGs) are required for efficient entry of HTLV-1. Here, the roles of HSPGs and GLUT-1 in HTLV-1 and HTLV-2 Env-mediated binding and entry into primary T cells were studied. Examination of the cell surface of activated primary T cells revealed that CD4(+) T cells, the primary target of HTLV-1, expressed significantly higher levels of HSPGs than CD8(+) T cells. Conversely, CD8(+) T cells, the primary target of HTLV-2, expressed GLUT-1 at dramatically higher levels than CD4(+) T cells. Under these conditions, the HTLV-2 surface glycoprotein (SU) binding and viral entry were markedly higher on CD8(+) T cells while HTLV-1 SU binding and viral entry were higher on CD4(+) T cells. Binding studies with HTLV-1/HTLV-2 SU recombinants showed that preferential binding to CD4' T cells expressing high levels of HSPGs mapped to the C-terminal portion of SU. Transfection studies revealed that overexpression of GLUT-1 in CD4(+) T cells increased HTLV-2 entry, while expression of HSPGs on CD8(+) T cells increased entry of HTLV-1. These studies demonstrate that HTLV-1 and HTLV-2 differ in their T-cell entry requirements and suggest that the differences in the in vitro cellular tropism for transformation and in vivo pathobiology of these viruses reflect different interactions between their Env proteins and molecules on CD4' and CD8(+) T cells involved in entry.