Tishon A, Oldstone M B
Am J Pathol. 1987 Jan;126(1):61-72.
Abnormal glucose metabolism (hyperglycemia and/or aberrant glucose tolerance test) occurred over the life-times of mice persistently infected with lymphocytic choriomeningitis virus (LCMV). Persistent infection could be initiated in both newborn and adult mice. For newborns, inoculation with any of several strains of LCMV (Armstrong, E350, Pasteur, Traub or WE) caused continuous infection, but such infection of adults required a selected lymphotropic variant of LCMV Armstrong (Clone 13). Throughout these animals' lives, viral materials (nucleic acid sequences and proteins) accumulated in multiple tissues, including the beta-cells of the islets of Langerhans; infectious virus was present in blood and tissues, and the LCMV-specific H-2 restricted CTL response was poor. Adult mice that had been inoculated with virus as newborns displayed neither histopathologic injury nor infiltrates of mononuclear cells in the islets of Langerhans despite moderate viral replication in beta-cells. In contrast, mice inoculated as adults with Clone 13 LCMV consistently developed inflammatory infiltrates in perivascular spaces of the islets of Langerhans, and their beta-cells expressed LCMV antigens. Addition of a subdiabetogenic dose of streptozotocin, a specific beta-cell toxin, magnified the virus-induced abnormality in glucose metabolism. This indicated a potentiating role between persistent virus infection initiated at birth or in adulthood and an environmental factor in causing abnormalities in glucose metabolism.
在持续感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）的小鼠一生中，均出现了异常的葡萄糖代谢（高血糖和/或异常的葡萄糖耐量试验）。新生小鼠和成年小鼠均可引发持续感染。对于新生小鼠，接种几种LCMV毒株（阿姆斯特朗株、E350株、巴斯德株、特劳伯株或WE株）中的任何一种都会导致持续感染，但成年小鼠的这种感染需要选择LCMV阿姆斯特朗株的嗜淋巴细胞变体（克隆13）。在这些动物的整个生命过程中，病毒物质（核酸序列和蛋白质）在多个组织中积累，包括胰岛的β细胞；血液和组织中存在传染性病毒，且LCMV特异性的H-2限制性CTL反应较弱。尽管β细胞中有适度的病毒复制，但新生时接种病毒的成年小鼠在胰岛中既未表现出组织病理学损伤，也没有单核细胞浸润。相比之下，成年时接种克隆13 LCMV的小鼠在胰岛的血管周围间隙中持续出现炎性浸润，且其β细胞表达LCMV抗原。添加亚致糖尿病剂量的链脲佐菌素（一种特异性β细胞毒素）可放大病毒诱导的葡萄糖代谢异常。这表明出生时或成年时开始的持续病毒感染与环境因素在导致葡萄糖代谢异常方面具有协同作用。
