Expression of glucose transporter 1 confers susceptibility to human T-cell leukemia virus envelope-mediated fusion
Expression of glucose transporter 1 confers susceptibility to human T-cell leukemia virus envelope-mediated fusion
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DOI：
10.1128/jvi.79.7.4150-4158.2005
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发表时间：
2005-04-01
影响因子：
5.4
通讯作者：
Sutton, RE
中科院分区：
文献类型：
--
作者：
Coskun, AK;Sutton, RE
人类T细胞白血病病毒1型（HTLV-1）是第一个人类逆转录病毒鉴定，并导致成人T细胞白血病/淋巴瘤和热带痉挛性下肢轻瘫/HTLV-1相关的脊髓病，以及其他疾病。在体外，HTLV-1具有极其广泛的宿主细胞嗜性，因为它能够感染大多数哺乳动物细胞类型，尽管同时病毒滴度保持相对较低。尽管经过多年的研究，直到最近才发现一种真正的候选细胞受体，葡萄糖转运蛋白1（glut-1）。尽管显示glut-1特异性结合HTLV-1和HTLV-2包膜糖蛋白的胞外域，这是可逆的，用针对glut-1的小干扰RNA，在表达glut-1时细胞对HTLV的易感性没有建立。在这里，我们表明，在相对耐药MDBK细胞中的glut-1的表达赋予增加的易感性，HTLV-1和HTLV-2假型颗粒。glut-1也显著增加了MDBK细胞在暴露于HTLV-1后的合胞体形成。另一项试验也证明了在glut-1存在下HTLV-1的细胞融合。综上所述，这些结果提供了额外的证据表明，glut-1是HTLV的受体。
Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus identified and causes both adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-1-associated myelopathy, among other disorders. In vitro, HTLV-1 has an extremely broad host cell tropism in that it is capable of infecting most mammalian cell types, although at the same time viral titers remain relatively low. Despite years of study, only recently has a bona fide candidate cellular receptor, glucose transporter 1 (glut-1), been identified. Although glut-1 was shown to bind specifically to the ectodomain of HTLV-1 and HTLV-2 envelope glycoproteins, which was reversible with small interfering RNA directed against glut-1, cellular susceptibility to HTLV upon expression of glut-1 was not established. Here we show that expression of glut-1 in relatively resistant MDBK cells conferred increased susceptibility to both HTLV-1- and HTLV-2-pseudotyped particles. glut-1 also markedly increased syncytium formation in MDBK cells after exposure to HTLV-1. Another assay also demonstrated HTLV-1 envelope-cell fusion in the presence of glut-1. Taken together, these results provide additional evidence that glut-1 is a receptor for HTLV.