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136 HTLV-2 Tax-2 Transactivator Increases the Expression and the Function of its Inhibitor CIITA, the Master Regulator of HLA-II Gene Transcription

Orlandi, Chiara; Tosi, Giovanna; Accolla, Roberto S

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 55
doi: 10.1097/01.qai.0000397323.41869.f7
Abstracts
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Department of Clinical and Biological Sciences, University of Insubria, Varese (Italy)

We previously showed that CIITA, the HLA Class-II transactivator, inhibits the transcriptional function of Tax-2 and, consequently, the replication of HTLV-2 virus in human susceptible B and T cells.

Here, we show for the first time that CIITA and Tax-2 interact in vivo and, that this interaction involves two independent regions of CIITA molecule. The physical interaction between the two transactivators may be at the basis of the observed functional effect on HTLV-2 viral replication. On the other side, Tax-2 might also influence the functional activity of CIITA. Thus we asked whether Tax-2 could affect the CIITA-dependent HLA-II expression. Expressing vectors of CIITA and Tax-2 were co-transfected in 293T cells and the cell surface expression of HLA molecules was evaluated by cytofluorometry. We observed that Tax-2 alone does not affect HLA-I or HLA-II-DR expression, whereas it increases CIITA-mediated expression of HLA-II-DR. Interestingly, in the presence of Tax-2, the expression of exogenous CIITA is significantly increased in a dose-dependent manner. Tax-2 affects also CIITA ability of interacting with NF-YB, component of the HLA-II enhanceosome, important for the recruitment of CIITA on HLA-II promoters. We ruled out a possible transcriptional effect of Tax-2 on CMV promoter driving the expression of CIITA, because Tax-2 does not increase the accumulation of CIITA internal fragment and other proteins transcribed from the same CMV promoter.

Preliminary data suggest that the increasing accumulation of CIITA molecule is the result of a slight extention of CIITA protein half-life induced by Tax-2.

Together with our previous observation that CIITA inhibits Tax-2 function, these findings might indicate that HTLV-2 virus exploits CIITA to negatively control its genes transcription and to decrease the production of new virions. This could be a new mechanism for the virus to remain latent in infected cells.

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.