Retroviral Oncogenesis Laboratory, INSERM-U758 Human Virology, Lyon, France.
Viruses. 2011 Aug;3(8):1374-94. doi: 10.3390/v3081374. Epub 2011 Aug 8.
Innate immunity plays a critical role in the host response to a viral infection. The innate response has two main functions. First, it triggers effector mechanisms that restrict the infection. Second, it primes development of the adaptive response, which completes the elimination of the pathogen or of infected cells. In vivo, HTLV-1 infects T lymphocytes that participate in adaptive immunity but also monocytes and dendritic cells that are major players in innate immunity. Herein, we will review the interplay between HTLV-1 and innate immunity. Particular emphasis is put on HTLV-1-induced alteration of type-I interferon (IFN-I) function. In vitro, the viral Tax protein plays a significant role in the alteration of IFN synthesis and signaling. Despite this, IFN-I/AZT treatment of Adult T-cell Leukemia/Lymphoma (ATLL) patients leads to complete remission. We will discuss a model in which exogenous IFN-I could act both on the microenvironment of the T-cells to protect them from infection, and also on infected cells when combined with other drugs that lead to Tax down-regulation/degradation.
先天免疫在宿主对病毒感染的反应中起着至关重要的作用。先天免疫有两个主要功能。首先,它触发限制感染的效应机制。其次,它启动适应性反应的发展,从而完成病原体或受感染细胞的清除。在体内,HTLV-1 感染参与适应性免疫的 T 淋巴细胞,但也感染先天免疫的主要参与者——单核细胞和树突状细胞。在此,我们将回顾 HTLV-1 与先天免疫之间的相互作用。特别强调的是 HTLV-1 诱导的 I 型干扰素(IFN-I)功能改变。在体外,病毒 Tax 蛋白在 IFN 合成和信号转导的改变中起着重要作用。尽管如此,IFN-I/阿扎胞苷治疗成人 T 细胞白血病/淋巴瘤(ATLL)患者会导致完全缓解。我们将讨论一个模型,其中外源性 IFN-I 可以既作用于 T 细胞的微环境以保护它们免受感染,也可以与导致 Tax 下调/降解的其他药物结合作用于受感染的细胞。