CYTOKINE-INDUCED EXPRESSION OF HIV-1 IN A CHRONICALLY INFECTED PROMONOCYTE CELL-LINE
CYTOKINE-INDUCED EXPRESSION OF HIV-1 IN A CHRONICALLY INFECTED PROMONOCYTE CELL-LINE
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DOI：
10.1126/science.3313729
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发表时间：
1987-11-06
期刊：
影响因子：
56.9
通讯作者：
FAUCI, AS
中科院分区：
文献类型：
--
作者：
FOLKS, TM;JUSTEMENT, J;FAUCI, AS
建立了细胞因子诱导的慢性感染的幼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。亲本幼单核细胞系 U937 长期感染 HIV-1，并从该细胞系衍生出克隆 U1。 U1显示出HIV-1的最小组成型表达，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和单独的重组粒细胞/巨噬细胞集落刺激因子显着上调。重组白细胞介素-1 (IL-1)、IL-2、干扰素-γ和肿瘤坏死因子-α。并没有上调病毒表达。伴随细胞因子诱导的 HIV-1 上调，膜结合的 IL-1.β 表达。在没有其他表面膜蛋白诱导的情况下，在 U1 中被选择性诱导。该细胞因子上调 IL-1.beta。在未感染的亲本 U937 细胞系中未见。这些研究对于理解从潜伏或低水平的 HIV-1 感染进展为有效感染并导致免疫抑制的机制具有重要意义。此外，该模型还可用于描述 HIV-1 感染调节细胞基因表达的潜在机制。
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.