The replication of HTLV-2 and the expression of HLA class II transcriptional activator (CIITA) are inversely correlated

Background: HTLV-2 is mitogenic for CD341 hematopoietic precursors and this effect is inhibited by HLA class II molecules (HLA-II) on the envelope. The aim of this study was to investigate the role of HLA-II in the phases of infection. Methods: The experimental system was designed by using HLA-II-positive and HLA-II-negative cells as targets for infection. As HLA-II negative targets, T-cell lines and B-cell mutants that have lost expression of HLA-II were used. To understand CIITA/HTLV-2 Tax interaction a transfection system was optimized in HeLa cells. Results: The extent of HTLV-2 replication is correlated with low or absent expression of HLA-II. HLA-II negative mutants segregated into two distinct clusters: permissive and non permissive for viral replication. Closer analysis revealed a correlation between the rate of expression of the AIR-1 encoded CIITA and inhibition of viral replication.On the contrary,HLA-II negative mutants supported HTLV-2 replication, this correlates with CIITA expression but not with HLA expression.Analysis of CIITA/HTLV-2 Tax interactions revealed that transcription of HTLV-LTR increased in HeLa cells only in the presence of Tax-2 and was reduced in a dose-dependentway by increasing CIITA. Conclusions: These results indicate that sustained expression of CIITA in HTLV-2-susceptible targets may down-regulate viral expression and open new ways to study the retrovirus replication in man.