Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Front Immunol. 2022 Aug 26;13:915805. doi: 10.3389/fimmu.2022.915805. eCollection 2022.
The main obstacle to cure HIV-1 is the latent reservoir. Antiretroviral therapy effectively controls viral replication, however, it does not eradicate the latent reservoir. Latent CD4 T cells are extremely rare in HIV-1 infected patients, making primary CD4 T cell models of HIV-1 latency key to understanding latency and thus finding a cure. In recent years several primary CD4 T cell models of HIV-1 latency were developed to study the underlying mechanism of establishing, maintaining and reversing HIV-1 latency. In the search of biomarkers, primary CD4 T cell models of HIV-1 latency were used for bulk and single-cell transcriptomics. A wealth of information was generated from transcriptome analyses of different primary CD4 T cell models of HIV-1 latency using latently- and reactivated HIV-1 infected primary CD4 T cells. Here, we performed a pooled data-analysis comparing the transcriptome profiles of latently- and reactivated HIV-1 infected cells of 5 primary CD4 T cell models of HIV-1 latency and 2 studies of reactivated HIV-1 infected primary CD4 T cells from HIV-1 infected individuals. Identifying genes that are differentially expressed between latently- and reactivated HIV-1 infected primary CD4 T cells could be a more successful strategy to better understand and characterize HIV-1 latency and reactivation. We observed that natural ligands and coreceptors were predominantly downregulated in latently HIV-1 infected primary CD4 T cells, whereas genes associated with apoptosis, cell cycle and HLA class II were upregulated in reactivated HIV-1 infected primary CD4 T cells. In addition, we observed 5 differentially expressed genes that co-occurred in latently- and reactivated HIV-1 infected primary CD4 T cells, one of which, MSRB2, was found to be differentially expressed between latently- and reactivated HIV-1 infected cells. Investigation of primary CD4 T cell models of HIV-1 latency that mimic the state remains essential for the study of HIV-1 latency and thus providing the opportunity to compare the transcriptome profile of latently- and reactivated HIV-1 infected cells to gain insights into differentially expressed genes, which might contribute to HIV-1 latency.
治愈 HIV-1 的主要障碍是潜伏储库。抗逆转录病毒疗法能有效控制病毒复制，但不能根除潜伏储库。HIV-1 感染者的潜伏 CD4 T 细胞极其罕见，因此建立 HIV-1 潜伏的原代 CD4 T 细胞模型对于理解潜伏和寻找治愈方法至关重要。近年来，人们开发了几种 HIV-1 潜伏的原代 CD4 T 细胞模型，用于研究建立、维持和逆转 HIV-1 潜伏的潜在机制。在寻找生物标志物的过程中，使用 HIV-1 潜伏的原代 CD4 T 细胞模型进行了 bulk 和单细胞转录组学研究。使用潜伏和再激活的 HIV-1 感染的原代 CD4 T 细胞对不同的 HIV-1 潜伏的原代 CD4 T 细胞模型进行转录组分析，产生了大量信息。在这里，我们对 5 种 HIV-1 潜伏的原代 CD4 T 细胞模型和 2 项来自 HIV-1 感染者的再激活 HIV-1 感染的原代 CD4 T 细胞的研究中潜伏和再激活的 HIV-1 感染的原代 CD4 T 细胞的转录组谱进行了汇总数据分析。鉴定潜伏和再激活的 HIV-1 感染的原代 CD4 T 细胞之间差异表达的基因可能是更好地理解和描述 HIV-1 潜伏和再激活的更成功策略。我们观察到，天然配体和核心受体在潜伏的 HIV-1 感染的原代 CD4 T 细胞中主要下调，而与细胞凋亡、细胞周期和 HLA Ⅱ类相关的基因在再激活的 HIV-1 感染的原代 CD4 T 细胞中上调。此外，我们观察到 5 个在潜伏和再激活的 HIV-1 感染的原代 CD4 T 细胞中共表达的差异表达基因，其中一个，MSRB2，在潜伏和再激活的 HIV-1 感染的细胞中存在差异表达。对模拟 HIV-1 潜伏状态的原代 CD4 T 细胞模型的研究仍然是 HIV-1 潜伏研究的关键，这为比较潜伏和再激活的 HIV-1 感染细胞的转录组谱提供了机会，从而深入了解差异表达的基因，这些基因可能有助于 HIV-1 潜伏。
