BackgroundImmunity against pathogens evolved through complex mechanisms that only for sake of simplicity are defined as innate immunity and adaptive immunity. Indeed innate and adaptive immunity are strongly intertwined each other during evolution. The complexity is further increased by intrinsic mechanisms of immunity that rely on the action of intracellular molecules defined as restriction factors (RFs) that, particularly in virus infections, counteract the action of pathogen gene products acting at different steps of virus life cycle.Main body and conclusionHere we provide an overview on the nature and the mode of action of restriction factors involved in retrovirus infection, particularly Human T Leukemia/Lymphoma Virus 1 (HTLV-1) infection. As it has been extensively studied by our group, special emphasis is given to the involvement of the MHC class II transactivator CIITA discovered in our laboratory as regulator of adaptive immunity and subsequently as restriction factor against HIV-1 and HTLV-1, a unique example of dual function linking adaptive and intrinsic immunity during evolution. We describe the multiple molecular mechanisms through which CIITA exerts its restriction on retroviruses. Of relevance, we review the unprecedented findings pointing to a concerted action of several restriction factors such as CIITA, TRIM22 and TRIM19/PML in synergizing against retroviral replication. Finally, as CIITA profoundly affects HTLV-1 replication by interacting and inhibiting the function of HTLV-1 Tax-1 molecule, the major viral product associated to the virus oncogenicity, we also put forward the hypothesis of CIITA as counteractor of HTLV-1-mediated cancer initiation.

中文翻译：

---

人类逆转录病毒感染的限制因素和前所未有的 CIITA 案例作为针对 HTLV-1 的内在和适应性免疫的纽带

背景针对病原体的免疫是通过复杂的机制进化而来的，为了简单起见，这些机制被定义为先天免疫和适应性免疫。事实上，先天免疫和适应性免疫在进化过程中相互紧密交织。免疫的内在机制进一步增加了复杂性，这些机制依赖于被定义为限制因子 (RF) 的细胞内分子的作用，特别是在病毒感染中，它会抵消病原体基因产物在病毒生命周期不同阶段的作用。 主体和结论在此我们概述了参与逆转录病毒感染，特别是人类 T 白血病/淋巴瘤病毒 1 (HTLV-1) 感染的限制因子的性质和作用方式。正如我们小组广泛研究的那样，特别强调了我们实验室发现的 MHC II 类反式激活因子 CIITA 作为适应性免疫调节剂的参与，随后作为针对 HIV-1 和 HTLV-1 的限制因子，这是进化过程中适应性和内在免疫双重功能联系的独特例子. 我们描述了 CIITA 对逆转录病毒施加限制的多种分子机制。相关的是，我们回顾了前所未有的发现，这些发现表明 CIITA、TRIM22 和 TRIM19/PML 等几个限制因素在协同对抗逆转录病毒复制方面的协同作用。最后，由于 CIITA 通过相互作用和抑制 HTLV-1 Tax-1 分子（与病毒致癌性相关的主要病毒产物）的功能来深刻影响 HTLV-1 复制，