Sun Jiangfeng, Barbeau Benoit, Tremblay Michel J
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario and Faculty of Medicine, Laval University, Que., Canada.
Virus Res. 2006 Jun;118(1-2):120-9. doi: 10.1016/j.virusres.2005.10.025. Epub 2006 Jan 18.
An important increase in luciferase activity was detected following co-culture of Jurkat T cells transiently transfected with an HTLV-I-LTR-driven reporter construct with HIV-1- and HTLV-I-infected cells. Production of infectious HTLV-I and expression of the HTLV-I envelope were not required for this HIV-1-dependent induction while it was severely hampered by anti-gp120 and anti-CD4 antibodies. The HTLV-I Tax protein and the TRE1 repeats were found to be necessary for the HIV-1-mediated enhancement of HTLV-I LTR activity in the co-culture assay. As these results suggested triple fusion events involving all three cell types and the intracellular transfer of Tax, we labelled each cell line with a distinct fluorescent probe. Through confocal microscopy, a number of resulting syncytia and cell clusters were indeed observed to be positive for all three probes. We are proposing a model in which HIV-1-mediated syncytium formation between HIV-1- and HTLV-I-infected cells and uninfected T cells forms a "bridge" or "tunnel" through which Tax from the HTLV-I-infected cells can diffuse and activate HTLV-I-LTR transcription.
在用HTLV-I-LTR驱动的报告基因构建体瞬时转染的Jurkat T细胞与HIV-1和HTLV-I感染细胞共培养后，检测到荧光素酶活性有显著增加。这种依赖HIV-1的诱导不需要产生有感染性的HTLV-I和HTLV-I包膜的表达，而抗gp120和抗CD4抗体则严重阻碍了这种诱导。在共培养试验中，发现HTLV-I Tax蛋白和TRE1重复序列对于HIV-1介导的HTLV-I LTR活性增强是必需的。由于这些结果提示了涉及所有三种细胞类型的三重融合事件以及Tax的细胞内转移，我们用不同的荧光探针标记了每个细胞系。通过共聚焦显微镜观察，确实观察到许多形成的多核巨细胞和细胞簇对所有三种探针均呈阳性。我们提出了一个模型，其中HIV-1介导的HIV-1和HTLV-I感染细胞与未感染T细胞之间的多核巨细胞形成一个“桥”或“通道”，HTLV-I感染细胞中的Tax可以通过这个通道扩散并激活HTLV-I-LTR转录。
