Fazakerley J K, Southern P, Bloom F, Buchmeier M J
Department of Neuropharmacology, Research Institute of Scripps Clinic, La Jolla, California 92037.
J Gen Virol. 1991 Jul;72 ( Pt 7):1611-25. doi: 10.1099/0022-1317-72-7-1611.
By the application of in situ hybridization to thin sections of paraffin-embedded tissues we have been able to determine with high resolution the cell types containing lymphocytic choriomeningitis virus nucleic acid in the tissues of persistently infected mice. We confirm and extend previous observations of virus persistence in the brain, lung, liver, kidney, pancreas, thyroid and reticuloendothelial system. In addition, we demonstrate for the first time persistence of viral nucleic acid in specific cell types in the thymus, lymph nodes, testes and bladder, and the adrenal, parathyroid and salivary glands; the cell types infected were observed in several animals. In lymphoid tissue, viral nucleic acid was predominantly located in the T cell-dependent areas of the spleen and lymph nodes; it was also present in cells of the thymic medulla. This has important implications for the deficiency in T cell function observed in persistently infected mice. In the testes, viral nucleic acid was detected in spermatogonia but not differentiating spermatocytes and therefore, in this tissue at least, persistence is related to the state of differentiation of the cell. Endocrine and exocrine dysfunctions have been described in persistently infected mice and we report that the highest levels of viral nucleic acid were found in the adrenal gland. The infection of endocrine and exocrine tissue was not pantropic, specific cell types expressed viral nucleic acid in each tissue. In the adrenal cortex, cells of the zona reticularis and zona fasciculata but not the zona glomerulosa were positive, whereas in the adrenal medulla viral nucleic acid was predominantly localized to adrenalin-secreting cells. Infection of the renal tubules, transitional epithelium of the bladder and the ducts of the salivary gland indicates the likely sites of virus production for the dissemination of arenavirus infections.
通过将原位杂交技术应用于石蜡包埋组织的薄片，我们得以高分辨率地确定持续感染小鼠组织中含有淋巴细胞性脉络丛脑膜炎病毒核酸的细胞类型。我们证实并扩展了先前关于病毒在脑、肺、肝、肾、胰腺、甲状腺和网状内皮系统中持续存在的观察结果。此外，我们首次证明病毒核酸在胸腺、淋巴结、睾丸、膀胱以及肾上腺、甲状旁腺和唾液腺的特定细胞类型中持续存在；在几只动物中观察到了被感染的细胞类型。在淋巴组织中，病毒核酸主要位于脾脏和淋巴结中依赖T细胞的区域；它也存在于胸腺髓质的细胞中。这对于在持续感染小鼠中观察到的T细胞功能缺陷具有重要意义。在睾丸中，在精原细胞中检测到病毒核酸，但在分化中的精母细胞中未检测到，因此，至少在这个组织中，病毒持续存在与细胞的分化状态有关。在持续感染的小鼠中已经描述了内分泌和外分泌功能障碍，我们报告在肾上腺中发现了最高水平的病毒核酸。内分泌和外分泌组织的感染并非泛嗜性的，每种组织中的特定细胞类型表达病毒核酸。在肾上腺皮质中，网状带和束状带的细胞呈阳性，而球状带的细胞则为阴性，而在肾上腺髓质中，病毒核酸主要定位于分泌肾上腺素的细胞中。肾小管、膀胱的移行上皮和唾液腺导管的感染表明沙粒病毒感染传播的可能病毒产生部位。
