SLOW, PERSISTENT REPLICATION OF LENTIVIRUSES - ROLE OF TISSUE MACROPHAGES AND MACROPHAGE PRECURSORS IN BONE-MARROW
SLOW, PERSISTENT REPLICATION OF LENTIVIRUSES - ROLE OF TISSUE MACROPHAGES AND MACROPHAGE PRECURSORS IN BONE-MARROW
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DOI：
10.1073/pnas.82.20.7086
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
GHOTBI, Z
中科院分区：
文献类型：
--
作者：
GENDELMAN, HE;NARAYAN, O;GHOTBI, Z
慢病毒，如绵羊的Visna病毒，是一种非致癌逆转录病毒，在长期潜伏后会导致缓慢进展的疾病。早期对Visna的研究表明，该病潜伏期长与组织中持续产生微量病毒有关，而病毒可以通过从淋巴组织和炎症器官的外植体培养单核细胞和巨噬细胞获得。在这项研究中，通过两只经气管内接种病毒的绵羊，探讨了巨噬细胞在慢病毒感染中的作用。当对石蜡包埋组织切片进行检查时，我们发现，病毒复制几乎完全与肺泡间区选定的巨噬细胞、肺、淋巴结和脾中的炎性渗出细胞中的感染有关。虽然大量的肺泡巨噬细胞含有病毒RNA，但这些细胞中很少产生病毒。虽然这种最低产量的病毒复制类型提供了感染速度缓慢的原因，但在终末分化的、短暂的巨噬细胞中的限制性复制无法解释动物中持续的病毒复制。随着在骨髓中发现受感染的巨噬细胞前体簇，发现了一种持久的机制。巨噬细胞前体细胞在病毒-靶细胞回路中提供了一个重要的缺失环节，可能是潜伏感染细胞的储存库，这些细胞使慢病毒在动物和人类中的感染永久化。
Lentiviruses, as exemplified by visna virus of sheep, are nononcogenic retroviruses that cause slowly progressive diseases after prolonged periods of incubation. Earlier studies on visna have shown that the long incubation period of the disease is associated with constant production of minimal quantities of virus in tissues, whereas virus could be obtained by culturing monocytes and macrophages from explants of lymphatic tissues and inflamed organs. In this study the role of macrophages in lentivirus infection was explored using two sheep that were intrabronchially inoculated with virus. When sections of paraffin-embedded tissue, processed by a recently described technique which combines immunocytochemistry for the identification of macrophages and in situ hybridization for identification of viral nucleic acid, were examined, we found that virus replication is associated almost exclusively with infection in selected populations of macrophages in the interalveolar region of the alveoli, in inflammatory exudate cells in the lung, in lymph nodes, and in the spleen. Although large numbers of alveolar macrophages had viral RNA, few of these cells produced virus. While this minimally productive type of viral replication provides an explanation for the slow pace of the infection, restricted replication in terminally differentiated, short-lived macrophages does not explain persistent virus replication in the animal. With the discovery of clusters of infected macrophage precursors in the bone marrow, a mechanism for persistence was found. The macrophage precursor cells provide an important missing link in the virus-target-cell circuit and may be the reservoir of latently infected cells which perpetuate lentivirus infections in both animals and humans.