Tam P E, Schmidt A M, Ytterberg S R, Messner R P
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
J Lab Clin Med. 1994 Mar;123(3):346-56.
Mice infected with the Tucson strain of coxsackievirus B1 (CVB1T) develop chronic T cell-mediated polymyositis that is manifest as the acute infection resolves and is characterized by hindquarter weakness and muscle inflammation. This model system was used to study persistence of CVB1T RNA by using reverse transcriptase-polymerase chain reaction (RT-PCR). For the most part, RNA persistence reflected the myotropic and neurotropic nature of the virus. At 1 month after infection, infectious virus was not detected in muscle, but persistent viral RNA was found in both skeletal and cardiac muscle, brain, and spinal cord. The kidney was weakly positive for viral RNA, whereas the liver and spleen were negative. Hindquarter muscle was assayed for persistent viral RNA at 1, 3, 6, 9, and 12 months after infection. In a few cases, persistent viral RNA was detected as late as 12 months after infection. The incidence of persistent viral RNA was high at 1 month after infection and gradually declined until, at 6 months and beyond, it was maintained in 3% to 12% of the muscles tested. Long-term viral RNA persistence was not more common in severely weak animals. However, the degree of hindquarter weakness that developed by 1 month was static thereafter and did not change over the 12-month study period. In contrast, separate experiments revealed that typical mononuclear cell (MNC) infiltration of muscle followed a time course similar to that of viral RNA persistence, peaking at 1 month and gradually resolving by 6 months. Infiltrating polymorphonuclear leukocytes (PMNs) and mast cells were present at 3 to 12 months after infection, signifying that some inflammatory activity remained. Other signs of myopathy that persisted for 12 months included a lack of muscle regeneration, variations in fiber size, and myofiber atrophy with increased perimysial and endomysial connective tissue. These results demonstrate that coxsackievirus RNA can persist in muscle for extended periods of time and are compatible with the idea that persistent virus is involved in maintaining the chronic MNC inflammation observed in murine polymyositis.
感染柯萨奇病毒B1图森株（CVB1T）的小鼠会发展为慢性T细胞介导的多发性肌炎，在急性感染消退时显现出来，其特征为后肢无力和肌肉炎症。该模型系统被用于通过逆转录聚合酶链反应（RT-PCR）研究CVB1T RNA的持续性。在很大程度上，RNA的持续性反映了病毒的嗜肌性和嗜神经性。感染后1个月，在肌肉中未检测到传染性病毒，但在骨骼肌、心肌、脑和脊髓中发现了持续性病毒RNA。肾脏的病毒RNA呈弱阳性，而肝脏和脾脏为阴性。在感染后1、3、6、9和12个月对后肢肌肉进行持续性病毒RNA检测。在少数情况下，感染后12个月仍检测到持续性病毒RNA。感染后1个月持续性病毒RNA的发生率很高，并逐渐下降，直到6个月及以后，在所检测的肌肉中有3%至12%维持阳性。长期病毒RNA持续性在严重虚弱的动物中并不更常见。然而，1个月时出现的后肢无力程度此后保持稳定，在12个月的研究期内没有变化。相比之下，单独的实验表明，肌肉中典型的单核细胞（MNC）浸润的时间进程与病毒RNA持续性相似，在1个月时达到峰值，并在6个月时逐渐消退。感染后3至12个月存在浸润的多形核白细胞（PMN）和肥大细胞，表明仍有一些炎症活动。持续12个月的其他肌病迹象包括缺乏肌肉再生、纤维大小变化以及肌纤维萎缩伴肌束膜和肌内膜结缔组织增加。这些结果表明，柯萨奇病毒RNA可在肌肉中长期持续存在，这与持续性病毒参与维持小鼠多发性肌炎中观察到的慢性MNC炎症的观点相符。
