The MHC-II transactivator CIITA, a restriction factor against oncogenic HTLV-1 and HTLV-2 retroviruses: similarities and differences in the inhibition of Tax-1 and Tax-2 viral transactivators.

Greta Forlani,Roberto S Accolla,Rawan Abdallah,Giovanna Tosi

doi:10.3389/fmicb.2013.00234

Abstract

The activation of CD4+ T helper cells is strictly dependent on the presentation of antigenic peptides by MHC class II (MHC-II) molecules. MHC-II expression is primarily regulated at the transcriptional level by the AIR-1 gene product CIITA (class II transactivator). Thus, CIITA plays a pivotal role in the triggering of the adaptive immune response against pathogens. Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against HTLV-1 (human T cell lymphotropic virus type 1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively. Here we review our findings on CIITA-mediated inhibition of viral replication and discuss similarities and differences in the molecular mechanisms by which CIITA specifically counteracts the function of Tax-1 and Tax-2 molecules. The dual function of CIITA as a key regulator of adaptive and intrinsic immunity represents a rather unique example of adaptation of host-derived factors against pathogen infections during evolution.

Highlights

Adaptive and innate immune responses represent the most powerful tool used by the host to counteract infectious agents
Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against human T cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively
In this review we provided an update on the anti-viral features that make CIITA a fundamental link between adaptive and intrinsic immunity against HTLV infections

Summary

INTRODUCTION

Adaptive and innate immune responses represent the most powerful tool used by the host to counteract infectious agents. Other modifications of CIITA, including acetylation, deacetylation, and ubiquitination (Spilianakis et al, 2000; Wu et al, 2009 and references therein), might have a major role in Tax-1-binding Such PTMs have been reported to affect the interaction of CIITA with cellular factors involved in MHC-II transcription (Greer et al, 2003) and the recruitment of either corepressors or coactivators on different promoters (Xu et al, 2008; Wu et al, 2009). Our findings suggest that CIITA-mediated inhibition of Tax activity could rely on the physical association between the two factors We know that this binding occurs off DNA, but it is still unclear whether Tax–CIITA complexes are recruited on the HTLV LTR (Figure 3A). While many investigations had assessed the contribution of NF-Y to class II transcription, no data regarding the specific role of

Proteins Function

CONCLUSION