Molecular Oncology Group, Lady Davis Institute-Jewish General Hospital, and Department of Microbiology, McGill University, Montreal, Canada H3T 1E2.
Cytokine Growth Factor Rev. 2011 Aug;22(4):197-210. doi: 10.1016/j.cytogfr.2011.08.002. Epub 2011 Sep 15.
Infection with the Human T-cell Leukemia virus type I (HTLV-1) retrovirus results in a number of diverse pathologies, including the aggressive, fatal T-cell malignancy adult T-cell leukemia (ATL) and the chronic, progressive neurologic disorder termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Worldwide, it is estimated there are 15-20 million HTLV-1-infected individuals; although the majority of HTLV-1-infected individuals remain asymptomatic carriers (AC) during their lifetime, 2-5% of AC develops either ATL or HAM/TSP, but never both. Regardless of asymptomatic status or clinical outcome, HTLV-1 carriers are at high risk of opportunistic infection. The progression to pathological HTLV-1 disease is in part attributed to the failure of the innate and adaptive immune system to control virus spread. The innate immune response against retroviral infection requires recognition of viral pathogen-associated molecular patterns (PAMPs) through pattern-recognition receptors (PRR) dependent pathways, leading to the induction of host antiviral and inflammatory responses. Recent studies have begun to characterize the interplay between HTLV-1 infection and the innate immune response and have identified distinct gene expression profiles in patients with ATL or HAM/TSP--upregulation of growth regulatory pathways in ATL and constitutive activation of antiviral and inflammatory pathways in HAM/STP. In this review, we provide an overview of the replicative lifecycle of HTLV-1 and the distinct pathologies associated with HTLV-1 infection. We also explore the innate immune mechanisms that respond to HTLV-1 infection, the strategies used by HTLV-1 to subvert these defenses and their contribution to HTLV-1-associated diseases.
感染人类 T 细胞白血病病毒 1 型（HTLV-1）逆转录病毒会导致多种病理变化，包括侵袭性致命的 T 细胞恶性肿瘤成人 T 细胞白血病（ATL）和慢性进行性神经疾病，称为 HTLV-1 相关脊髓病/热带痉挛性截瘫（HAM/TSP）。在全球范围内，估计有 1500 万至 2000 万 HTLV-1 感染者；尽管大多数 HTLV-1 感染者在其一生中仍为无症状携带者（AC），但 2%-5%的 AC 会发展为 ATL 或 HAM/TSP，但从未同时发展为两种疾病。无论是否处于无症状状态或临床结果如何，HTLV-1 携带者都有发生机会性感染的高风险。向病理性 HTLV-1 疾病的进展部分归因于先天和适应性免疫系统未能控制病毒传播。针对逆转录病毒感染的先天免疫反应需要通过模式识别受体（PRR）依赖途径识别病毒病原体相关分子模式（PAMP），从而诱导宿主抗病毒和炎症反应。最近的研究开始描述 HTLV-1 感染与先天免疫反应之间的相互作用，并在 ATL 或 HAM/TSP 患者中鉴定出不同的基因表达谱——ATL 中生长调节途径的上调和 HAM/STP 中抗病毒和炎症途径的组成性激活。在这篇综述中，我们概述了 HTLV-1 的复制生命周期以及与 HTLV-1 感染相关的不同病理变化。我们还探讨了先天免疫机制对 HTLV-1 感染的反应，HTLV-1 用来颠覆这些防御的策略及其对 HTLV-1 相关疾病的贡献。
