Clonal analysis suggests provirus expression in a subpopulation of human malignant trophoblast cells harbouring the human T cell lymphotropic virus type-I genome

Previous studies have indicated that the villous trophoblast may be involved in intrauterine HTLV-I infection. Although the data furnished by our group (Liu at al., 1995) have demonstrated that the human trophoblast-derived malignant cell lines JAR and JEG-3 are susceptible to HTLV-I, the infection, even after thorough analysis, appeared to be limited 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 dilution from the previously infected parental cultures. Of the three cell lines JAR-H2, JAR-H3, 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 to be lower by three orders of magnitude. Viral Tax protein displaying a typical intranuclear localization was found in 1-2% of JAR-H2 and JEG-H3 cells. Moreover, an altered phenotype characterized by multinucleated syncytia was observed in these cell cultures with the same frequency as Tax transactivator, implying a fusogenic activity of env protein. Infectious virus, however, could not be rescued from JAR-H2 or JEG-H3 clones by coculture with cord blood mononuclear cells. Our data suggest that trophoblast represents a susceptible, albeit a slightly permissive, host system for HTLV-I.