EXPRESSION OF ALTERNATIVELY SPLICED HUMAN T-LYMPHOTROPIC VIRUS TYPE-IPX MESSENGER-RNA IN INFECTED CELL-LINES AND IN PRIMARY UNCULTURED CELLS FROM PATIENTS WITH ADULT T-CELL LEUKEMIA LYMPHOMA AND HEALTHY CARRIERS

Although human T-cell lymphotropic virus type I (HTLV-I) is the etiolo gic agent of adult T-cell leukemia/lyumphoma (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 stu dies to readily detect HTLV-I RNA in infected individuals. By using th e reverse transcriptase-polymerase chain reaction, we detected spliced messages for the HTLV-I pX regulatory genes in primary uncultured cel ls from ATL patients and healthy asymptomatic carriers. In addition to the expected doubly spliced pX message, three alternatively spliced m RNAs were demonstrated (pX-DELTA-17, pX-p21rex, and pX-orfII mRNAs, wh ere 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 cod e for known and putative pX gene products. Among the transcripts is a monocistronic mRNA likely to code for p21rex (pX-p21rex mRNA). Since a lternative splicing of HTLV-I pX mRNA can be found in primary uncultur ed 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.