HIV Downregulates Interferon-Stimulated Genes in Primary Macrophages
HIV Downregulates Interferon-Stimulated Genes in Primary Macrophages
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DOI：
10.1089/jir.2012.0052
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发表时间：
2013-02-01
影响因子：
2.3
通讯作者：
Woelk, Christopher H.
中科院分区：
文献类型：
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作者：
Wie, Seong-Heon;Du, Pinyi;Woelk, Christopher H.
HIV能够超过先天免疫反应，包括干扰素（IFN）介导的免疫反应，以建立生产性感染。然而，原代巨噬细胞可以通过在病毒暴露前用I型IFN治疗来保护免受HIV感染。当HIV遇到已经暴露于IFN的细胞时，HIV调节I型IFN介导的先天免疫应答的能力仍然不清楚。最佳预处理时间（12 h）和最有效的HIV抑制剂（e.例如，在一个实施例中，IFN-α 2和IFN-ω）来研究HIV调节已建立的I型IFN应答的能力。然后在用I型IFN处理的原代巨噬细胞与用IFN处理然后感染HIV的原代巨噬细胞之间比较整个转录组水平的基因表达。尽管HIV不能建立强有力的感染，但该病毒能够下调许多IFN刺激的基因（ISG），其倍数变化大于1.5（即，AXL、IFI 27、IFI 44、IFI 44 L、ISG 15、OAS 1、OAS 3和XAF 1）。通过实时定量聚合酶链反应证实了HIV的存在对OAS 1的下调。总之，尽管IFN预处理显著抑制了HIV复制，但病毒能够下调已知抗病毒ISG的转录（例如，例如，在一个实施例中，IFI 44、ISG 15和OAS 1）。
HIV is able to outpace the innate immune response, including that mediated by interferon (IFN), to establish a productive infection. Primary macrophages, however, may be protected from HIV infection by treatment with type I IFN before virus exposure. The ability of HIV to modulate the type I IFN-mediated innate immune response when it encounters a cell that has already been exposed to IFN remains poorly defined. The optimal pretreatment time (12 h) and the most potent HIV-inhibitors (e. g., IFN-alpha 2 and -omega) were identified to investigate the ability of HIV to modulate an established type I IFN response. Gene expression at the level of the entire transcriptome was then compared between primary macrophages treated with type I IFNs, as opposed to treated with IFNs and then infected with HIV. Although HIV was not able to establish a robust infection, the virus was able to downregulate a number of IFN-stimulated genes (ISGs) with a fold change greater than 1.5 (i.e., AXL, IFI27, IFI44, IFI44L, ISG15, OAS1, OAS3, and XAF1). The downregulation of OAS1 by the presence of HIV was confirmed by real-time quantitative polymerase chain reaction. In conclusion, even though HIV replication is significantly inhibited by IFN pretreatment, the virus is able to downregulate the transcription of known antiviral ISGs (e. g., IFI44, ISG15, and OAS1).