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单核细胞系巨噬细胞1:一种用于研究HIV-1在单核吞噬细胞系列人类细胞中感染情况的新型体外模型系统。

Mono Mac 1: a new in vitro model system to study HIV-1 infection in human cells of the mononuclear phagocyte series.

作者信息

Genois N, Robichaud G A, Tremblay M J

机构信息

Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Pavilion CHUL, and Département de Biologie Médicale, Faculté de Médecine, Université Laval, Ste-Foy, Canada.

出版信息

J Leukoc Biol. 2000 Dec;68(6):854-64.

Abstract

Throughout the years, most researchers have used continuous cell lines as in vitro models to evaluate the immunopathogenesis of human immunodeficiency virus type-1 (HIV-1) infection. Unfortunately, the most commonly used monocytoid malignant cells have not been shown to adequately mimic primary human monocyte-derived macrophages, at least with respect to HIV-1 infection. The Mono Mac 1 cell line has been defined as a model system for studying biochemical, immunological, and genetic functions of human cells of the monocyte/macrophage lineage. In this study, we have investigated whether Mono Mac 1 represents an in vitro culture system for HIV-1 infection. Flow cytometric analyses revealed that Mono Mac 1 are positive for the HIV-1 primary receptor (CD4), as well as for the coreceptors (CXCR4, CCR5, and CCR3). Infectivity experiments conducted with recombinant luciferase-encoding and fully infectious viruses demonstrated that Mono Mac 1 can support a highly productive infection with both macrophage- and dual-tropic isolates of HIV-1. Furthermore, differentiation of such cells led to a marked increase in virus production. Data from semiquantitative polymerase chain reaction analysis and mobility shift assays indicated that enhanced virus production in differentiated Mono Mac 1 cells was most likely related to an increase in nuclear translocation of NF-kappaB. Mono Mac 1 can thus be considered as a human monocytoid cell line representing a proper in vitro system for studying the complex interactions between HIV-1 and cells of the monocyte/macrophage lineage.

摘要

多年来,大多数研究人员一直使用连续细胞系作为体外模型来评估1型人类免疫缺陷病毒(HIV-1)感染的免疫发病机制。不幸的是,至少在HIV-1感染方面,最常用的单核细胞样恶性细胞尚未被证明能充分模拟原代人单核细胞衍生的巨噬细胞。Mono Mac 1细胞系已被定义为研究单核细胞/巨噬细胞谱系人类细胞的生化、免疫和遗传功能的模型系统。在本研究中,我们调查了Mono Mac 1是否代表一种用于HIV-1感染的体外培养系统。流式细胞术分析显示,Mono Mac 1对HIV-1主要受体(CD4)以及共受体(CXCR4、CCR5和CCR3)呈阳性。用重组荧光素酶编码病毒和完全感染性病毒进行的感染性实验表明,Mono Mac 1可以支持HIV-1巨噬细胞嗜性和双嗜性分离株的高效感染。此外,这些细胞的分化导致病毒产生显著增加。半定量聚合酶链反应分析和迁移率变动分析的数据表明,分化的Mono Mac 1细胞中病毒产生的增加最可能与NF-κB核转位的增加有关。因此,Mono Mac 1可被视为一种人类单核细胞样细胞系,代表了一个用于研究HIV-1与单核细胞/巨噬细胞谱系细胞之间复杂相互作用的合适体外系统。

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