Macrophages are the major target cell for HIV infection in long-term bone marrow culture and demonstrate dual susceptibility to lymphocytotropic and monocytotropic strains of HIV-1
Macrophages are the major target cell for HIV infection in long-term bone marrow culture and demonstrate dual susceptibility to lymphocytotropic and monocytotropic strains of HIV-1
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DOI：
10.1046/j.1365-2141.1996.4801017.x
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发表时间：
1996-04-01
影响因子：
6.5
通讯作者：
Gibson, FM
中科院分区：
文献类型：
--
作者：
Gill, V;Shattock, RJ;Gibson, FM
血液学异常通常见于感染艾滋病毒的患者。许多机制被认为有助于这种骨髓抑制，包括基质功能受损和祖细胞的直接感染。有证据表明，骨髓祖细胞和可能的基质细胞都对HIV感染开放，这增加了骨髓基质细胞可能作为HIV储存库的可能性。本研究调查了细胞的目标和在长期骨髓培养（LTBMC）中使用单和嗜淋巴细胞株的HIV-1的体外感染的基质的动力学。p24酶联免疫吸附试验（ELISA）和逆转录酶（RT）检测表明，间质可被HIV感染并释放感染性病毒粒子。免疫组化（APAAP）、免疫荧光双标（CD 68和p24）和电镜观察表明，感染的靶细胞是巨噬细胞，说明HIV可以感染LTBMC的间质，而且这种感染是生产性的，感染的主要靶细胞是骨髓巨噬细胞。与外周血来源的巨噬细胞相反，这些细胞对HIV-1的亲淋巴细胞和亲单核细胞株均敏感。这些数据表明，这些骨髓巨噬细胞可能是HIV的储存库。骨髓巨噬细胞的感染可能通过直接细胞间接触将HIV感染传递给发育中的祖细胞或通过改变基质支持正常发育的能力来影响造血。
Haematological abnormalities are often seen in patients infected with HIV. A number of mechanisms are thought to contribute to this bone marrow suppression, including impaired stromal function and direct infection of progenitor cells. Evidence suggests that both bone marrow progenitor cells and perhaps stromal cells are open to infection by HIV, which raises the possibility that bone marrow stromal cells may serve as a reservoir for HIV. This study investigated the cellular targets and kinetics of in vitro infection of stroma in long-term bone marrow culture (LTBMC) using both mono- and lymphocytotropic strains of HIV-1. p24 ELISA and reverse transcriptase (RT) assay demonstrated that stroma could be infected with HIV and release infectious virions. The target cells for infection were shown to be macrophages by immunohistochemistry (APAAP), dual immunofluorescence staining (using CD68 and p24) and electron microscopy.The data show that it was possible to infect stroma in LTBMC with HIV and that such infection was productive, The main target for infection was bone marrow macrophages. In contrast to peripheral blood derived macrophages, these cells were susceptible to both lymphocytotropic and monocytotropic strains of HIV-1. The data suggests that these bone marrow macrophages may act as a reservoir for HIV. Infection of bone marrow macrophages may affect haemopoiesis either by transmission of HIV infection to developing progenitor cells through direct cell-to-cell contact or by altering the ability of the stroma to support normal development.