Hashikura Yuuki, Umeki Kazumi, Umekita Kunihiko, Nomura Hajime, Yamada Akiteru, Yamamoto Ikuo, Hasegawa Hiroo, Yanagihara Katsunori, Okayama Akihiko
Department of Rheumatology, Infectious Diseases and Laboratory Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8102, Japan.
Hum Cell. 2017 Apr;30(2):117-123. doi: 10.1007/s13577-016-0156-4. Epub 2017 Jan 9.
In a previous study, we reported that an identical defective provirus had integrated into multiple sites of the genome of a representative human T-lymphotropic virus type 1 (HTLV-1) cell line, MT-2. A possible explanation for this may be the repeated infection of this defective provirus to a cell. Therefore, we attempted to determine whether a defective provirus could transmit during the co-culture of HTLV-1 uninfected human T-cell line, Jurkat, with MT-2 cells treated with mitomycin C. As a result, we established not only a cell line with the integration of one complete provirus, but also a cell line with the integration of one defective provirus. The rearrangement of the T-cell receptor -γ gene of these cell lines showed them to be derived from Jurkat cells. Both HTLV-1 Tax/Rex and HBZ RNA were detected in the cell line, which harbors a complete provirus. On the other hand, HBZ RNA and transcriptional product specific for the defective provirus were detected in the cell line, which harbors a defective HTLV-1 provirus only. These results suggested that a defective HTLV-1 provirus with large depletion of internal sequence could transmit to other cells. Moreover, the defective provirus can be transcriptionally active. This suggested the possibility that the defective HTLV-1 provirus found in the lymphocytes of HTLV-1 carriers and patients with adult T-cell leukemia may transmit to other T-cells in vivo. The results also suggested that defective provirus in HTLV-1 carriers could be functional and may play a role in leukemogenesis.
在之前的一项研究中，我们报道了一个相同的缺陷型前病毒已整合到代表性的1型人类嗜T淋巴细胞病毒（HTLV-1）细胞系MT-2基因组的多个位点。对此的一种可能解释是该缺陷型前病毒反复感染一个细胞。因此，我们试图确定在未感染HTLV-1的人类T细胞系Jurkat与经丝裂霉素C处理的MT-2细胞共培养期间，缺陷型前病毒是否能够传播。结果，我们不仅建立了一个整合有一个完整前病毒的细胞系，还建立了一个整合有一个缺陷型前病毒的细胞系。这些细胞系的T细胞受体-γ基因重排表明它们源自Jurkat细胞。在含有完整前病毒的细胞系中检测到了HTLV-1 Tax/Rex和HBZ RNA。另一方面，仅在含有缺陷型HTLV-1前病毒的细胞系中检测到了HBZ RNA和缺陷型前病毒特异性的转录产物。这些结果表明，内部序列大量缺失的缺陷型HTLV-1前病毒能够传播到其他细胞。此外，缺陷型前病毒具有转录活性。这提示在HTLV-1携带者和成人T细胞白血病患者淋巴细胞中发现的缺陷型HTLV-1前病毒可能在体内传播到其他T细胞。结果还表明，HTLV-1携带者中的缺陷型前病毒可能具有功能，并可能在白血病发生过程中发挥作用。
