CLONAL ANALYSIS SUGGESTS PROVIRUS EXPRESSION IN A SUBPOPULATION OF HUMAN-MALIGNANT TROPHOBLAST CELLS HARBORING THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I GENOME

Previous studies have indicated that the villous trophoblast may be in volved in intrauterine HTLV-I infection. Although the data furnished b y our group (Liu at al., 1995) have demonstrated that the human tropho blast-derived malignant cell lines JAR and JEG-3 are susceptible to HT LV-I, the infection, even after thorough analysis, appeared to be limi ted to expression at the transcriptional level. In the present report, we sought to explore virus expression at the single cell level using eight clonally selected cell lines which were derived by limiting dilu tion from the previously infected parental cultures. Of the three cell lines JAR-HS, JAR-HS, and JEG-H3, all of which harboured full-length provirus, only in two (JAR-H2 and JEG-H3) were the virus-specific tax/ rex and env transcripts demonstrated using RT-PCR. When compared with MT-2 cells, the detected steady-state levels of HTLV-I mRNA appeared t o be lower by three orders of magnitude. Viral Tax protein displaying a typical intranuclear localization was found in 1-2% of JAR-H2 and JE G-H3 cells. Moreover, an altered phenotype characterized by multinucle ated syncytia was observed in these cell cultures with the same freque ncy as Tax transactivator, implying a fusogenic activity of env protei n. Infectious virus, however, could not be rescued from JAR-H2 or JEG- H3 clones by coculture with cord blood mononuclear cells. Our data sug gest that trophoblast represents a susceptible, albeit a slightly perm issive, host system for HTLV-I.