Veselinovic Milena, Charlins Paige, Akkina Ramesh
Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO, 80523, USA.
Methods Mol Biol. 2016;1354:203-20. doi: 10.1007/978-1-4939-3046-3_14.
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.
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。