Comparative analysis of human microglial models for studies of HIV replication and pathogenesis.
Comparative analysis of human microglial models for studies of HIV replication and pathogenesis.
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DOI：
10.1186/s12977-020-00544-y
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发表时间：
2020-11-19
期刊：
影响因子：
3.3
通讯作者：
Spearman P
中科院分区：
文献类型：
--
作者：
Rai MA;Hammonds J;Pujato M;Mayhew C;Roskin K;Spearman P
尽管出现了高效抗逆转录病毒治疗，但艾滋病毒相关的神经认知障碍仍引起显著的发病率和死亡率。对HIV感染的基本机制和中枢神经系统的发病机制有更深入的了解是必要的。小胶质细胞是驻留在大脑中的髓样细胞，很容易被HIV感染，可能构成中枢神经系统的储存库。我们评估了两种小胶质模型细胞系（C20, HMC3）和两种原代细胞来源的小胶质细胞（单核细胞来源的小胶质细胞[MMG]和诱导多能干细胞来源的小胶质细胞[iPSC-MG]）作为研究hiv -小胶质细胞相互作用的潜在模型系统。除了C20和HMC3低表达或不表达CD45和CD11b外，所有四种小胶质模型细胞都表达典型的髓系标志物，并且所有四种细胞都表达小胶质特异性标志物P2RY12和TMEM119。然而，基因表达谱显示，MMG和iPSC-MG与原代人小胶质细胞紧密聚集在一起，而C20和HMC3彼此相似，但与原代人小胶质细胞差异很大。hiv相关基因的表达也显示出重要的差异，iPSC-MG和MMG表达相关基因的水平更接近初级小胶质细胞。iPSC-MG和MMG容易感染R5-tropic HIV，而C20和HMC3缺乏CD4，需要假分型才能感染。尽管有许多相似之处，但MMG和iPSC-MG的HIV复制动力学和siglec1捕获的HIV-1颗粒明显不同。MMG和iPSC-MG似乎是可行的小胶质细胞模型，它们对HIV感染敏感，与两种转化的小胶质细胞系相比，它们更接近真实的小胶质细胞。MMG和iPSC-MG在HIV复制和颗粒捕获方面的差异值得进一步研究。
HIV associated neurocognitive disorders cause significant morbidity and mortality despite the advent of highly active antiretroviral therapy. A deeper understanding of fundamental mechanisms underlying HIV infection and pathogenesis in the central nervous system is warranted. Microglia are resident myeloid cells of the brain that are readily infected by HIV and may constitute a CNS reservoir. We evaluated two microglial model cell lines (C20, HMC3) and two sources of primary cell-derived microglia (monocyte-derived microglia [MMG] and induced pluripotent stem cell-derived microglia [iPSC-MG]) as potential model systems for studying HIV-microglia interactions. All four microglial model cells expressed typical myeloid markers with the exception of low or absent CD45 and CD11b expression by C20 and HMC3, and all four expressed the microglia-specific markers P2RY12 and TMEM119. Marked differences were observed upon gene expression profiling, however, indicating that MMG and iPSC-MG cluster closely together with primary human microglial cells, while C20 and HMC3 were similar to each other but very different from primary microglia. Expression of HIV-relevant genes also revealed important differences, with iPSC-MG and MMG expressing relevant genes at levels more closely resembling primary microglia. iPSC-MG and MMG were readily infected with R5-tropic HIV, while C20 and HMC3 lack CD4 and require pseudotyping for infection. Despite many similarities, HIV replication dynamics and HIV-1 particle capture by Siglec-1 differed markedly between the MMG and iPSC-MG. MMG and iPSC-MG appear to be viable microglial models that are susceptible to HIV infection and bear more similarities to authentic microglia than two transformed microglia cell lines. The observed differences in HIV replication and particle capture between MMG and iPSC-MG warrant further study.
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耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
影响因子：
8.8
作者：
Askew K;Li K;Olmos-Alonso A;Garcia-Moreno F;Liang Y;Richardson P;Tipton T;Chapman MA;Riecken K;Beccari S;Sierra A;Molnár Z;Cragg MS;Garaschuk O;Perry VH;Gomez-Nicola D
通讯作者：
Gomez-Nicola D
影响因子：
7.3
作者：
Greter M;Lelios I;Croxford AL
通讯作者：
Croxford AL
影响因子：
5.9
作者：
Douvaras P;Sun B;Wang M;Kruglikov I;Lallos G;Zimmer M;Terrenoire C;Zhang B;Gandy S;Schadt E;Freytes DO;Noggle S;Fossati V
通讯作者：
Fossati V
影响因子：
3.2
作者：
Garcia-Mesa, Yoelvis;Jay, Taylor R.;Alvarez-Carbonell, David
通讯作者：
Alvarez-Carbonell, David
影响因子：
7.3
作者：
Milush JM;Chen HL;Atteberry G;Sodora DL
通讯作者：
Sodora DL