HTLV TYPE IIIB INFECTION OF HUMAN THYMIC EPITHELIAL-CELLS - VIRAL EXPRESSION CORRELATES WITH THE INDUCTION OF NF-KAPPA-B-BINDING ACTIVITY IN CELLS ACTIVATED BY CELL-ADHESION

Productive infection by the LAV strain has been demonstrated in T cell precursors at different stages of intrathymic development, while vira l replication in thymic epithelial cells is still controversial, In th is article we show that epithelial cell cultures derived from the medu llary component of normal thymus are infectable by HTLV-IIIB virus thr ough cell-free and lymphoid-mediated transmission. Free virus inoculum results in the integration of proviral copies undergoing poor replica tion, whereas lymphoid-mediated transmission leads to substantial vira l expression and the production of viral progeny able to secondary inf ect lymphoid cells. Interleukin 6 production and phenotype changes (in creased expression of MHC class I and ICAM-1) were induced in TE cells by contact with free virus or by adhesion to infected lymphoid cells. By contrast, NF-kappa B-binding activity on the HIV-1 LTR kappa B enh ancer element was upregulated only by contact with infected lymphoid c ells, but not with virus. The viral replication observed in TE cells a fter lymphoid-mediated transmission correlates with the upregulation o f NF-kappa B-binding activity. Interleukin 6 increased production and phenotype changes and increased NF-kappa B-binding activity were also induced by adhesion to uninfected lymphoid cells, demonstrating that l ymphoepithelial cell contacts can activate TE cells. These results dem onstrate that thymic epithelial cells are permissive to HIV infection and that viral replication in this cell lineage can be modulated by in tracellular signals delivered by adhesive contacts.