HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1 CAN INFECT PRIMARY RAT RETINALGLIAL-CELLS AND INDUCE GENE-EXPRESSION OF INFLAMMATORY CYTOKINES

Purpose. To examine whether or not retinal glial cells can be infected by human T-cell lymphotropic virus type 1 (HTLV-1) and test the possi bility that HTLV-l-infected retinal glial cells are involved in the pa thogenesis of HTLV-1 uveitis (HU). Methods. We tested infection of HTL V-1 by a standard co-culturing method using WKAH rat retinal glial cel ls and irradiated MT-2, a human T cell line that produces HTLV-1. Infe ction was confirmed by detecting the integrated HTLV-1 provirus, using polymerase chain reaction (PCR), viral gene expression, using reverse transcriptase-PCR (RT-PCR) and HTLV-1 p19 ELISA, and by identifying t he HTLV-1-infected glial cells by immunofluorescence cytochemistry and in situ hybridization. Changes in cytokine gene expression were studi ed by RT-PCR. Results. Using a semiquantitative PCR of HTLV-1 provirus sequence, we found that 2.6% of the retinal glial cells were infected at 3 days after infection, followed by a gradual decrease in the perc entage with an extended period of culture up to 4 weeks. This time cou rse of infection was also verified by RT-PCR and ELISA studies that de tect viral mRNA expression and protein production, respectively. Expre ssion of HTLV-1 gag protein and tax mRNA was detected in a part of gli al cells by indirect immunofluorescence cytochemistry and in situ hybr idization, respectively. RT-PCR analysis of cytokine gene expression r evealed that gene expression of IL-6, CINC-1 (Gro, KC), and TNF-alpha were induced in these cells, with a peak at 3 weeks after infection. C onclusion. These results provided supportive evidence for the theory t hat the infection of retinal glial cells by HTLV-1 and subsequent prod uction of inflammatory cytokines could be one contributing factor for the development of the unique clinical features of HU. A better unders tanding of the specific roles of the inflammatory cytokines in the pat hogenesis of HU would be beneficial in the treatment and control of th is disease.