HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model

人源化小鼠模型中,转基因 iPSC 衍生的中枢神经系统移植小胶质细胞的 HIV-1 感染

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作者:Alice K Min, Behnam Javidfar, Roy Missall, Donald Doanman, Madel Durens, Mara Graziani, Annika Mordelt, Samuele G Marro, Lotje de Witte, Benjamin K Chen, Talia H Swartz, Schahram Akbarian

Abstract

Our mouse model is a powerful tool for investigating the genetic mechanisms governing central nervous system (CNS) human immunodeficiency virus type-1 (HIV-1) infection and latency in the CNS at a single-cell level. A major advantage of our model is that it uses induced pluripotent stem cell-derived microglia, which enables human genetics, including gene function and therapeutic gene manipulation, to be explored in vivo, which is more challenging to study with current hematopoietic stem cell-based models for neuroHIV. Our transgenic tracing of xenografted human cells will provide a quantitative medium to develop new molecular and epigenetic strategies for reducing the HIV-1 latent reservoir and to test the impact of therapeutic inflammation-targeting drug interventions on CNS HIV-1 latency.

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