Infection of defective human T-lymphotropic virus type 1

• Published in: Human cell : official journal of Human Cell Research Society 2017-04, Vol.30 (2), p.117-123
• Main Authors: Hashikura, Yuuki, Umeki, Kazumi, Umekita, Kunihiko, Nomura, Hajime, Yamada, Akiteru, Yamamoto, Ikuo, Hasegawa, Hiroo, Yanagihara, Katsunori, Okayama, Akihiko
• Format: Article
• Language: English
• Subjects: Base Sequence; Biomedical and Life Sciences; Cell Biology; Cell culture; Cell Line; Gene rearrangement; Gene Rearrangement, T-Lymphocyte; Genomes; Gynecology; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - pathogenicity; Human T-lymphotropic virus 1 - physiology; Humans; Integration; Jurkat Cells - virology; Leukemogenesis; Life Sciences; Lymphocytes T; Mitomycin C; Oncology; Polymerase Chain Reaction - methods; Receptors, Antigen, T-Cell, gamma-delta - genetics; Reproductive Medicine; Research Article; Ribonucleic acid; RNA; Stem Cells; Surgery; T cell receptors; Transcription; Virus Integration
• ISSN: 1749-0774; 0914-7470; 1749-0774
• DOI: 10.1007/s13577-016-0156-4

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.