Expression of Alternatively Spliced Human T-Lymphotropic Virus Type I pX mRNA in Infected Cell Lines and in Primary Uncultured Cells from Patients with Adult T-Cell Leukemia/Lymphoma and Healthy Carriers

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-04, Vol.89 (7), p.3005-3009
• Main Authors: Berneman, Zwi N., Gartenhaus, Ronald B., Reitz, Marvin S., Blattner, William A., Manns, Angela, Hanchard, Barrie, Ikehara, Osamu, Gallo, Robert C., Klotman, Mary E.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Alternative splicing; Base Sequence; Cell lines; Cells, Cultured; Cellular biology; Deltaretrovirus Infections - genetics; Exons; Gene Expression; Genes, pX; Human T lymphotropic virus 1; Human T-lymphotropic virus 1 - genetics; Humans; In Vitro Techniques; Leukemia; Leukemia-Lymphoma, Adult T-Cell - genetics; Medical research; Messenger RNA; Molecular Sequence Data; Nucleotides; Oligodeoxyribonucleotides - chemistry; Oligonucleotide probes; Polymerase Chain Reaction; Reverse transcriptase polymerase chain reaction; Ribonucleic acid; RNA; RNA Splicing; RNA, Messenger - genetics; T lymphocytes; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.7.3005

Although human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), the role of viral gene expression in the progression to and maintenance of the leukemic state in vivo is unclear because of the inability of most previous studies to readily detect HTLV-I RNA in infected individuals. By using the reverse transcriptase-polymerase chain reaction, we detected spliced messages for the HTLV-I pX regulatory genes in primary uncultured cells from ATL patients and healthy asymptomatic carriers. In addition to the expected doubly spliced pX message, three alternatively spliced mRNAs were demonstrated (pXΔ17, pX-p21rex, and pX-orfII mRNAs, where orf = open reading frame). The same splice sites were shown in the messages from uncultured ATL cells and from the HTLV-I-producing C10/MJ cell line. Alternatively spliced pX mRNAs have the potential to code for known and putative pX gene products. Among the transcripts is a monocistronic mRNA likely to code for p21rex(pX-p21rexmRNA). Since alternative splicing of HTLV-I pX mRNA can be found in primary uncultured cells, it is likely to have a functional significance in vivo. This suggests possible roles for HTLV-I gene expression in the progression to and maintenance of ATL, as well as in the phase preceding it.