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This article is part of the supplement: 15th International Conference on Human Retroviruses: HTLV and Related Viruses

Open Access Open Badges Meeting abstract

The MHC-II transactivator CIITA, a viral restriction factor inhibiting the replication of Human T-Cell Lymphotropic Virus Type 1

Giovanna Tosi1*, Greta Forlani1, Vibeke Andresen2, Marco Turci3, Umberto Bertazzoni3, Genoveffa Franchini4 and Roberto S Accolla1

Author Affiliations

1 Department of Experimental Medicine, University of Insubria, Varese, 21100, Italy

2 Institute of Medicine, Hematology section, University of Bergen, Bergen, Norway

3 Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy

4 Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD, USA

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Retrovirology 2011, 8(Suppl 1):A171  doi:10.1186/1742-4690-8-S1-A171

The electronic version of this article is the complete one and can be found online at:

Published:6 June 2011

© 2011 Tosi et al; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Meeting abstract

Human T-cell Lymphotropic Virus type-1 (HTLV-1) is the causative agent of an aggressive malignancy of CD4+ T lymphocytes. It is believed that the viral transactivator Tax-1 is a major player in T-cell transformation. Thus, targeting Tax-1 protein is regarded as a possible strategy to arrest viral replication and ultimately to counteract neoplastic transformation.

Here, we demonstrated that CIITA, the master regulator of MHC class II gene transcription, inhibits HTLV-1 replication by blocking the transactivating function of Tax-1. Co-immunoprecipitation experiments have shown that CIITA and Tax-1 physically interact in vivo and that the first 108 amino acids of Tax-1 were necessary for this binding. Two adjacent regions (1-252 and 253-410) of CIITA bound independently to Tax-1, but only region 1-252 mediated Tax-1 inhibition, in agreement with the fact that CIITA residues from positions 64-124 were required to block Tax-1 transactivation. CIITA inhibitory action on Tax-1 function correlated with the nuclear localization of CIITA and was independent of the transcription factor NF-YB, previously involved in CIITA-mediated inhibition of Tax-2 of HTLV-2, a virus with still elusive pathogenic action. Furthermore, CIITA severely impaired the physical and functional interaction of Tax-1 with the cellular co-activator PCAF, which is required for the optimal activation of HTLV-1 promoter. Accordingly, the over-expression of PCAF restored Tax-1-dependent transactivation of the viral LTR promoter inhibited by CIITA.

These findings strongly support our original observation that CIITA, beside increasing the antigen-presenting function for pathogen antigens, acts as an endogenous restriction factor against human retroviruses by blocking virus replication and spreading.