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在人源化小鼠中模拟HIV-1黏膜传播与预防

Modeling HIV-1 Mucosal Transmission and Prevention in Humanized Mice.

作者信息

Veselinovic Milena, Charlins Paige, Akkina Ramesh

机构信息

Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO, 80523, USA.

出版信息

Methods Mol Biol. 2016;1354:203-20. doi: 10.1007/978-1-4939-3046-3_14.

Abstract

The new generation humanized mice (hu-mice) that permit continuous de novo generation of human hematopoietic cells have led to novel strategies in studying HIV-1 pathogenesis, prevention and therapies. HIV-1 infection of hu-mice results in chronic viremia and CD4+ T cell loss, thus mimicking key aspects of the disease progression. In addition, the new generation hu-mice are permissive for HIV-1 sexual transmission by vaginal and rectal routes thus allowing in vivo efficacy testing of new anti-HIV-1 drugs for prevention. Two leading models are currently being used, namely the hu-HSC mice and the BLT mice. Here we describe the methodology for generating both hu-HSC and BLT mice and their use in the study of HIV-1 transmission and prevention of infection by topical and oral administration of anti-retroviral drugs. Practical aspects of the methodologies are emphasized.

摘要

新一代能够持续从头生成人类造血细胞的人源化小鼠(hu-小鼠),为研究HIV-1发病机制、预防和治疗带来了新策略。hu-小鼠感染HIV-1会导致慢性病毒血症和CD4+ T细胞损失,从而模拟疾病进展的关键方面。此外,新一代hu-小鼠允许通过阴道和直肠途径进行HIV-1性传播,从而能够对预防新型抗HIV-1药物进行体内疗效测试。目前正在使用两种主要模型,即hu-HSC小鼠和BLT小鼠。在此,我们描述了生成hu-HSC和BLT小鼠的方法,以及它们在研究HIV-1传播和通过局部和口服抗逆转录病毒药物预防感染方面的应用。重点强调了这些方法的实际操作方面。

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