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Global mapping of the macrophage-HIV-1 transcriptome reveals that productive infection induces remodeling of the host cell DNA and chromatin

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180273 | GEO | 2021/07/21

REPOSITORIES: GEO

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Project description:The aquatic orthomyxovirus infectious salmon anemia virus (ISAV) is an important pathogen for salmonid aquaculture, however little is known about protective and pathological host responses to infection. We have investigated intracellular responses during cytopathic ISAV infection in the macrophage-like Atlantic salmon kidney (ASK) cell line by microarray analysis (1.8K SFA2.0 immunochip) and a functional assay for glutathione. Gene transcription changed rapidly and consistently with time and with minor differences between two virus isolates. While several pro-inflammatory and antiviral immune genes were induced, genes involved in cell signaling and integrity were down-regulated, suggesting isolation of infected cells from cell-to-cell interaction and responses to external signals. Differential expression of genes regulating cell cycle and apoptosis implied opposite cues from host cell and virus. This was in pace with massive down-regulation of genes involved in biosynthesis and processing of nucleotides and nucleic acids. Significant down-regulation of several genes involved in metabolism of reactive oxygen species suggested increased oxidative stress, which was confirmed by a functional assay showing reduced levels of glutathione during infection. Testing of expression data against a microarray database containing diverse experiments revealed candidate marker genes for ISAV infection. Our findings provide novel insight into cellular host responses and determinants for acute cytopathic ISAV infection. Keywords: Infectious salmon anemia virus (ISAV); Host response; Molecular pathology; Microarray; Macrophage; Oxidative stress ASK cells infected with ISAV isolate 2 and 4 and mock-infected were cultured in triplicates and total RNA pooled from each at the following time-points post-infection; 1, 3 and 5 days. For microarray analysis, single-slide hybridisation was applied between infected RNA (Cy5 labelled) and control RNA (Cy3 labelled) for each time-point. Results were verified by real-time qPCR.

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Global mapping of the macrophage-HIV-1 transcriptome reveals that productive infection induces remodeling of the host cell DNA and chromatin

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