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人类嗜 T 淋巴细胞病毒 1 型感染与发病机制:细胞和动物模型的新见解。

HTLV-1 Infection and Pathogenesis: New Insights from Cellular and Animal Models.

机构信息

Laboratory of General Pathology and Immunology "Giovanna Tosi", Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy.

Department of Biosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy.

出版信息

Int J Mol Sci. 2021 Jul 27;22(15):8001. doi: 10.3390/ijms22158001.

Abstract

Since the discovery of the human T-cell leukemia virus-1 (HTLV-1), cellular and animal models have provided invaluable contributions in the knowledge of viral infection, transmission and progression of HTLV-associated diseases. HTLV-1 is the causative agent of the aggressive adult T-cell leukemia/lymphoma and inflammatory diseases such as the HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Cell models contribute to defining the role of HTLV proteins, as well as the mechanisms of cell-to-cell transmission of the virus. Otherwise, selected and engineered animal models are currently applied to recapitulate in vivo the HTLV-1 associated pathogenesis and to verify the effectiveness of viral therapy and host immune response. Here we review the current cell models for studying virus-host interaction, cellular restriction factors and cell pathway deregulation mediated by HTLV products. We recapitulate the most effective animal models applied to investigate the pathogenesis of HTLV-1-associated diseases such as transgenic and humanized mice, rabbit and monkey models. Finally, we summarize the studies on STLV and BLV, two closely related HTLV-1 viruses in animals. The most recent anticancer and HAM/TSP therapies are also discussed in view of the most reliable experimental models that may accelerate the translation from the experimental findings to effective therapies in infected patients.

摘要

自人类 T 细胞白血病病毒 1(HTLV-1)被发现以来,细胞和动物模型在病毒感染、传播和 HTLV 相关疾病进展的知识方面做出了非常宝贵的贡献。HTLV-1 是侵袭性成人 T 细胞白血病/淋巴瘤和炎症性疾病(如 HTLV-1 相关脊髓病/热带痉挛性截瘫(HAM/TSP))的病原体。细胞模型有助于确定 HTLV 蛋白的作用以及病毒细胞间传播的机制。此外,还应用了选定和工程化的动物模型来在体内重现 HTLV-1 相关发病机制,并验证病毒治疗和宿主免疫反应的有效性。在这里,我们回顾了用于研究病毒-宿主相互作用、细胞限制因子和 HTLV 产物介导的细胞途径失调的当前细胞模型。我们总结了最有效的动物模型,用于研究 HTLV-1 相关疾病的发病机制,如转基因和人源化小鼠、兔和猴模型。最后,我们总结了关于 STLV 和 BLV 的研究,这两种是动物中与 HTLV-1 密切相关的病毒。还讨论了最新的抗癌和 HAM/TSP 疗法,因为最可靠的实验模型可能会加速从实验结果到感染患者有效治疗的转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7707/8347336/a32fcb1388d3/ijms-22-08001-g001.jpg

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