Onodera T, Toniolo A, Ray U R, Jenson A B, Knazek R A, Notkins A L
J Exp Med. 1981 Jun 1;153(6):1457-73. doi: 10.1084/jem.153.6.1457.
Mice infected with reovirus type 1 developed transient diabetes and a runting syndrome. The diabetes was characterized by hyperglycemia, abnormal glucose tolerance tests, and hypoinsulinemia. Inflammatory cells and viral antigens were found in the islets of Langerhans, and virus particles were seen in alpha, beta, and delta cells. The runting syndrome consisted of retarded growth, oily hair, alopecia, and steatorrhea. Inflammatory cells and viral antigens were found in the anterior, but not posterior pituitary. Electron microscopy revealed virus particles in growth hormone (GH)-producing cells and radioimmunoassay showed that the concentration of GH in the blood was decreased. Examination of sera from infected mice revealed autoantibodies that, by immunofluorescence, reacted with cytoplasmic antigens in the islets of Langerhans, anterior pituitary, and gastric mucosa of uninfected mice. Absorption studies and enzyme-linked immunosorbent assays designed to identify the reactive antigens showed that some of the autoantibodies were directed against insulin and others against GH. Reovirus type 3, in contrast to reovirus type 1, did not induce autoantibodies to GH. By use of recombinant viruses, the segment of the reovirus genome responsible for the induction of autoantibodies to GH was identified. Virus containing the S1 gene segment from reovirus type 1, which codes for the sigma 1 polypeptide (i.e., hemagglutinin), infected cells in the anterior pituitary and induced autoantibodies to GH, whereas virus containing the S1 gene segment from reovirus type 3 failed to infect cells in the anterior pituitary and did not induce autoantibodies to GH. We conclude that reovirus type 1 infection can lead to polyendocrinopathy and autoimmunity and that the S1 gene segment is required for the induction of autoantibodies to GH.
感染1型呼肠孤病毒的小鼠会出现短暂性糖尿病和发育迟缓综合征。糖尿病的特征为高血糖、葡萄糖耐量试验异常和低胰岛素血症。在胰岛中发现了炎症细胞和病毒抗原，在α细胞、β细胞和δ细胞中可见病毒颗粒。发育迟缓综合征包括生长迟缓、毛发油腻、脱发和脂肪痢。在前叶垂体中发现了炎症细胞和病毒抗原，但后叶垂体中未发现。电子显微镜检查显示生长激素（GH）分泌细胞中有病毒颗粒，放射免疫分析表明血液中GH浓度降低。对感染小鼠血清的检测发现了自身抗体（通过免疫荧光法检测），这些自身抗体与未感染小鼠的胰岛、前叶垂体和胃黏膜中的细胞质抗原发生反应。旨在鉴定反应性抗原的吸收研究和酶联免疫吸附试验表明，一些自身抗体针对胰岛素，另一些针对GH。与1型呼肠孤病毒不同，3型呼肠孤病毒不会诱导针对GH的自身抗体。通过使用重组病毒，确定了呼肠孤病毒基因组中负责诱导针对GH的自身抗体的片段。含有1型呼肠孤病毒S1基因片段（该片段编码σ1多肽，即血凝素）的病毒感染前叶垂体中的细胞并诱导产生针对GH的自身抗体，而含有3型呼肠孤病毒S1基因片段的病毒未能感染前叶垂体中的细胞，也未诱导产生针对GH的自身抗体。我们得出结论，1型呼肠孤病毒感染可导致多内分泌腺病和自身免疫，并且S1基因片段是诱导针对GH的自身抗体所必需的。
