Folks T M, Justement J, Kinter A, Dinarello C A, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Science. 1987 Nov 6;238(4828):800-2. doi: 10.1126/science.3313729.
A model system for cytokine-induced up-regulation of human immunodeficiency virus type 1 (HIV-1) expression in chronically infected promonocyte clones was established. The parent promonocyte cell line U937 was chronically infected with HIV-1 and from this line a clone, U1, was derived. U1 showed minimal constitutive expression of HIV-1, but virus expression was markedly up-regulated by a phytohemagglutinin-induced supernatant containing multiple cytokines and by recombinant granulocyte/macrophage colony-stimulating factor alone. Recombinant interleukin-1 (IL-1), IL-2, interferon-gamma, and tumor necrosis factor-alpha did not up-regulate virus expression. Concomitant with the cytokine-induced up-regulation of HIV-1, expression of membrane-bound IL-1 beta was selectively induced in U1 in the absence of induction of other surface membrane proteins. This cytokine up-regulation of IL-1 beta was not seen in the uninfected parent U937 cell line. These studies have implications for the understanding of the mechanism of progression from a latent or low-level HIV-1 infection to a productive infection with resulting immunosuppression. In addition, this model can be used to delineate the potential mechanisms whereby HIV-1 infection regulates cellular gene expression.
建立了一种细胞因子诱导慢性感染的原单核细胞克隆中人类免疫缺陷病毒1型（HIV-1）表达上调的模型系统。原单核细胞系U937被HIV-1慢性感染，并从该系中获得了一个克隆U1。U1显示出极低的HIV-1组成型表达，但病毒表达被含有多种细胞因子的植物血凝素诱导的上清液以及单独的重组粒细胞/巨噬细胞集落刺激因子显著上调。重组白细胞介素-1（IL-1）、IL-2、干扰素-γ和肿瘤坏死因子-α均未上调病毒表达。与细胞因子诱导的HIV-1上调同时，在未诱导其他表面膜蛋白的情况下，U1中选择性地诱导了膜结合IL-1β的表达。在未感染的亲本U937细胞系中未观察到这种细胞因子对IL-1β的上调作用。这些研究对于理解从潜伏或低水平HIV-1感染进展为导致免疫抑制的 productive感染的机制具有重要意义。此外，该模型可用于阐明HIV-1感染调节细胞基因表达的潜在机制。
