Background 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. Results 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. Conclusions 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.

中文翻译：

---

用于研究 HIV 复制和发病机制的人类小胶质细胞模型的比较分析

背景 尽管出现了高效抗逆转录病毒疗法，但与 HIV 相关的神经认知障碍仍会导致显着的发病率和死亡率。有必要更深入地了解中枢神经系统中 HIV 感染和发病机制的基本机制。小胶质细胞是大脑中的常驻骨髓细胞，很容易被 HIV 感染，并且可能构成 CNS 储存库。我们评估了两种小胶质细胞模型细胞系（C20、HMC3）和两种原代细胞衍生小胶质细胞来源（单核细胞衍生小胶质细胞 [MMG] 和诱导多能干细胞衍生小胶质细胞 [iPSC-MG]）作为研究 HIV 的潜在模型系统-小胶质细胞相互作用。结果除 C20 和 HMC3 的 CD45 和 CD11b 表达低或不表达外，所有四种小胶质细胞模型细胞均表达典型的髓系标志物，并且所有四个都表达了小胶质细胞特异性标记 P2RY12 和 TMEM119。然而，在基因表达谱上观察到显着差异，表明 MMG 和 iPSC-MG 与原代人小胶质细胞紧密聚集在一起，而 C20 和 HMC3 彼此相似但与原代小胶质细胞非常不同。HIV 相关基因的表达也揭示了重要差异，iPSC-MG 和 MMG 表达的相关基因水平更接近于初级小胶质细胞。iPSC-MG 和 MMG 很容易感染 R5-tropic HIV，而 C20 和 HMC3 缺乏 CD4，需要假型感染。尽管有许多相似之处，但在 MMG 和 iPSC-MG 之间，Siglec-1 的 HIV 复制动力学和 HIV-1 颗粒捕获显着不同。结论 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，并且比两种转化的小胶质细胞系与真正的小胶质细胞具有更多的相似性。在 MMG 和 iPSC-MG 之间观察到的 HIV 复制和粒子捕获差异值得进一步研究。