The diversity of the structure and genomic integration sites of HTLV-1 provirus in MT-2 cell lines

• Published in: Human cell : official journal of Human Cell Research Society 2016-07, Vol.29 (3), p.122-129
• Main Authors: Hashikura, Yuuki, Umeki, Kazumi, Umekita, Kunihiko, Nomura, Hajime, Yamamoto, Ikuo, Hasegawa, Hiroo, Yanagihara, Katsunori, Okayama, Akihiko
• Format: Article
• Language: English
• Subjects: Base Sequence; Biomedical and Life Sciences; Cell Biology; Cell Line - virology; Coculture Techniques; Genome, Viral - genetics; Gynecology; Human T-lymphotropic virus 1 - genetics; Humans; Leukemia-Lymphoma, Adult T-Cell - virology; Leukocytes; Life Sciences; Oncology; Proviruses - genetics; Reproductive Medicine; Research Article; Stem Cells; Surgery; Virus Integration - genetics
• ISSN: 1749-0774; 1749-0774
• DOI: 10.1007/s13577-016-0136-8

A human T-lymphotropic virus Type 1 (HTLV-1) positive cell line, MT-2, derived from human cord leukocytes co-culturing with adult T cell leukemia/lymphoma (ATL) cells is commonly used in HTLV-1 research; however, the details of provirus integrated in MT-2 genome have not yet been characterized. In this study, five types of HTLV-1 proviral sequences were detected in 11 different sites of the genome in a reference MT-2 cell line. The five types of HTLV-1 proviral sequences were one complete proviral genome, two types of proviruses with deletion of large internal viral sequences (5.3 and 3.9 kB), one provirus with a large deletion (6.2 kB) from 5′LTR to position 6257, and one provirus of LTR only. The provirus with identical deletion of large internal viral sequence (5.3 kB) was found to be integrated into six different sites (chromosomes). A complete provirus and three of four types of defective provirus were consistently detected in two other MT-2 cell lines cultured in different laboratories. Not only Tax/Rex RNA and HBZ RNA, but also the transcriptional product for a specific defective provirus, were detectable in all three MT-2 cell lines. Because it has been reported that defective provirus is frequently detected in ATL cells, these results may be important in understanding the mechanism of HTLV-1 proviral polymorphism, which may be related to leukemogenesis. In addition, the large variation in integrated HTLV-1 proviruses makes it important for researchers to exercise caution in their assessment and interpretation of results using MT-2 cell lines.