Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Québec, Canada.
Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada.
Sci Rep. 2017 Jul 12;7(1):5238. doi: 10.1038/s41598-017-05566-9.
It has been proposed that macrophages could serve as long-lived compartments for HIV-1 infection under in vivo situations because these cells are resistant to the virus-mediated cytopathic effect, produce progeny virus over extended periods of time and are localized in tissues that are often less accessible by treatment. Comprehensive experimental studies are thus needed to characterize the HIV-1-induced modulation of host genes in these myeloid lineage cells. To shed light on this important issue, we performed comparative analyses of mRNA expression levels of host genes in uninfected bystander and HIV-1-infected human macrophages using an infectious reporter virus construct coupled with a large-scale RNA sequencing approach. We observed a rapid differential expression of several host factors in the productively infected macrophage population including genes regulating DNA replication factors and chromatin remodeling. A siRNA-mediated screening study to functionally identify host determinants involved in HIV-1 biology has provided new information on the virus molecular regulation in macrophages.
据提议，在体内情况下，巨噬细胞可能作为 HIV-1 感染的长寿隔室，因为这些细胞对病毒介导的细胞病变效应具有抗性，能够在较长时间内产生子代病毒，并定位于治疗通常难以到达的组织中。因此，需要进行全面的实验研究来描述这些髓系细胞中 HIV-1 诱导的宿主基因调节。为了阐明这个重要问题，我们使用感染性报告病毒构建体和大规模 RNA 测序方法，对未感染旁观者和 HIV-1 感染的人巨噬细胞中的宿主基因的 mRNA 表达水平进行了比较分析。我们观察到在产毒感染的巨噬细胞群体中，包括调节 DNA 复制因子和染色质重塑的基因在内的几种宿主因子迅速发生差异表达。siRNA 介导的筛选研究对功能鉴定参与 HIV-1 生物学的宿主决定因素，为巨噬细胞中的病毒分子调控提供了新信息。
