Delamarre L, Rosenberg A R, Pique C, Pham D, Dokhélar M C
URA 1156 CNRS, Institut Gustave Roussy, Villejuif, France.
J Virol. 1997 Jan;71(1):259-66. doi: 10.1128/JVI.71.1.259-266.1997.
Human T-leukemia virus type 1 (HTLV-1) envelope glycoproteins play a major role in viral transmission, which in the case of this virus occurs almost exclusively via cell-to-cell contact. Until very recently, the lack of an HTLV-1 infectivity assay precluded the determination of the HTLV-1 protein domains required for infectivity. Here, we describe an assay which allows the quantitative evaluation of HTLV-1 cell-to-cell transmission in a single round of infection. Using this assay, we demonstrate that in this system, cell-to-cell transmission is at least 100 times more efficient than transmission with free viral particles. We have examined 46 surface (SU) glycoprotein mutants in order to define the amino acids of the HTLV-1 SU glycoprotein required for full infectivity. We demonstrate that these amino acids are distributed along the entire length of the SU glycoprotein, including the N-terminus and C-terminus regions, which have not been previously defined as being important for HTLV-1 glycoprotein function. For most of the mutated glycoproteins, the capacity to mediate cell-to-cell transmission is correlated with the ability to induce formation of syncytia. This result indicates that the fusion capacity is the main factor responsible for infectivity mediated by the HTLV-1 SU envelope glycoprotein, as is the case for other retroviral glycoproteins. However, other factors must also intervene, since two of the mutated glycoproteins were correctly fusogenic but could not mediate cell-to-cell transmission. Existence of this phenotype shows that capacity for fusion is not sufficient to confer infectivity, even in cell-to-cell transmission, and could suggest that postfusion events involve the SU.
人类T淋巴细胞白血病病毒1型（HTLV-1）包膜糖蛋白在病毒传播中起主要作用，对于这种病毒而言，传播几乎仅通过细胞间接触发生。直到最近，由于缺乏HTLV-1感染性检测方法，无法确定感染所需的HTLV-1蛋白结构域。在此，我们描述了一种检测方法，可在单次感染中对HTLV-1细胞间传播进行定量评估。使用该检测方法，我们证明在这个系统中，细胞间传播的效率比游离病毒颗粒传播至少高100倍。我们检测了46个表面（SU）糖蛋白突变体，以确定HTLV-1 SU糖蛋白完全感染所需的氨基酸。我们证明这些氨基酸分布在SU糖蛋白的全长上，包括之前未被定义为对HTLV-1糖蛋白功能重要的N端和C端区域。对于大多数突变的糖蛋白，介导细胞间传播的能力与诱导多核巨细胞形成的能力相关。这一结果表明，融合能力是HTLV-1 SU包膜糖蛋白介导感染的主要因素，其他逆转录病毒糖蛋白也是如此。然而，其他因素也必定起作用，因为有两个突变的糖蛋白具有正确的融合能力，但不能介导细胞间传播。这种表型的存在表明，即使在细胞间传播中，融合能力也不足以赋予感染性，这可能表明融合后事件涉及SU。
