HTLV2 influence on pathways regulating proliferation and death in B cell line BJAB

Background: We have demonstrated that T cell derived HTLV-2 Mo strain is anti-apoptotic and mitogenic for CD34! hematopoietic precursors (Casoli et al., Blood 91:2296-2304, 1998). This property is lost when the Mo strain is adapted to grow in a B cell host by the presence of large amounts of HLAII molecules. The interplay between regulation of HLA-II expression and viral replication is related to CIITA/Tax interactions (Casoli et al., Blood 103:995-1001, 2004). Methods: In order to study the HTLV virus/host cell interaction, the B cell line BJAB, expressing HLA-II molecules, and its Gu HTLV-2-infected counterpart are chosen as model systems. Both cell lines were tested for their cell surface expression of HLA-II and CIITA mRNA levels. Apoptotic phases and cell cycle were also investigated by flow cytometry. Results: In comparison of uninfected cells, BJAB-infected cells showed a drammatic decrease of HLA-DR expression in association with a low amount of CIITA transcript. HTLV-2- infected cells undergo G1 arrest and apoptosis, that reflect p19 Ag production. Both early and late apoptotic cells are detected in high percentage (40%). Conclusions: On BJAB cells HTLV-2 infection downregulates HLA-II expression by blocking CIITA gene transcription. In this cell line HTLV-2 replication induced G1 arrest and enhances apoptosis.