Tax-1 the transactivator of HTLV-1 (Human T cell Leukemia virus type 1) is functionally inhibited by the cellular factor CIITA and this correlates with a dramatic suppression of the viral replication

We show that the replication of HTLV-1, the most important human oncogenic retrovirus associated with the onset of an aggressive form of leukaemia in the adults, is inhibited by CIITA the master regulator of MHC-II genes transcription. This is due to the functional suppression of the viral transactivator Tax-1. Co-immunoprecipitation experiments reveal that CIITA and Tax-1 interact in vivo and that two regions of CIITA mediate this binding. One of them encompasses the short stretch of aminoacids at the N-term of CIITA that is required to block the transcriptional activity of Tax-1. Moreover, the over-expression of P\CAF, a cellular co-factor used by both CIITA and Tax-1 to activate transcription from their target promoters (MHC-II and HTLV-1LTR, respectively), can rescue Tax-1 transactivating function inhibited by CIITA. Preliminary results show that Tax-1-P\CAF interaction is significantly inhibited in the presence of CIITA suggesting a possible sequestration of P\CAF by CIITA or the inability of Tax-1 to interact with P\CAF when bound to CIITA. Together with our previous findings on a similar inhibitory action of CIITA on HTLV-2 and HIV-1 retrovirus replication, these results confirm that CIITA, beside its fundamental role in regulating antigen presentation and adaptive immunity, is also a natural viral restriction factor. We hypothesize a potential use of CIITA as a physiologic tool for novel therapeutic strategies against retroviral infections