PATHOGENESIS OF ALEUTIAN DISEASE VIRUS INFECTION

阿留申水貂病细小病毒（ADV）引起持续感染， 仅限于成年动物，并与以下疾病有关： 免疫调节 阿留申病（AD）的特征包括多克隆 高丙种球蛋白血症，浆细胞增多症，免疫复合物疾病， 间质性和肾小球肾炎以及极高水平的抗- ADV抗体。研究结果的范围类似于 a细胞因子应答的Th 2模式。 该项目的范围是 阐明ADV感染导致这种不寻常的 disorder. 我们发现细胞因子白细胞介素-6（IL-6）的水平随着时间的推移而增加。 感染ADV的水貂发病。 此外，IL-6的量 随着水貂AD的发展，mRNA也出现增加。 条件 IL-6在人类和小鼠中过表达，类似于临床病理学 成年水貂ADV感染图片。 不适当的生产IL- 6，可能还有其他细胞因子，在慢性ADV感染期间可能发挥作用。 在产生免疫紊乱中的作用。 这将是 与Th 2型免疫反应一致 转录分析表明，限制性ADV感染可能是 与衣壳蛋白合成减少或 非结构蛋白2（NS 2）。 已发现NS 2合成中断 在细胞类型中引起其他细小病毒的非允许性感染 具体的时尚。 受感染的水貂不会产生可检测到的抗体反应， 各种非结构（NS）蛋白的区域。 当塞拉 针对含有开放阅读框特异性的融合蛋白进行测试 对于NS蛋白的片段，我们发现了针对NS 1的抗体 特定区域和所有NS蛋白共有的氨基末端区域， 但对NS 2特异性ORF没有反应性。 制备的抗体 针对NS 2特异性ORF检测到正确大小的蛋白质 表明NS 2是一个真正的基因产物， 细胞 因此，NS 2在ADV过程中可能在体内不表达。 感染 这一发现可能暗示了神经细胞中NS 2合成的紊乱。 限制体内感染。

Aleutian mink disease parvovirus (ADV) causes a persistent infection that is restricted in adult animals and is associated with disturbances of immune regulation. Features of Aleutian disease (AD) include polyclonal hypergammaglobulinemia, plasmacytosis, immune complex disease, interstitial and glomerulonephritis and exceedingly high levels of anti- ADV antibodies. The spectrum of findings resembles those associated with a Th2 pattern of cytokine responses. The scope of this project is to elucidate mechanisms by which ADV infection results in this unusual disorder. We found that levels of the cytokine Interleukin-6 (IL-6) increased as mink infected with ADV develop disease. Furthermore, amounts of IL-6 mRNA also appeared to increase as mink developed AD. Conditions in which IL-6 is overexpressed in human and mice resemble the clinicopathologic picture of ADV infection in adult mink. Inappropriate production of IL- 6, and possibly other cytokines, during chronic ADV infection may play a role in the generation of the immune disorders. This would be consistent with a Th2 type of immune response. Analysis of transcription suggested that restricted ADV infection may be associated with reduced synthesis of either capsid proteins or nonstructural protein 2 (NS2). Disrupted NS2 synthesis has been found to cause nonpermissive infection for other parvoviruses in a cell type specific fashion. Infected mink do not generate a detectable antibody response against all regions of the various nonstructural (NS) proteins. When sera were tested against fusion proteins containing open reading frames specific for segments of the NS proteins, we found antibodies directed against NS1 specific regions and the amino-terminal region common to all NS proteins, but no reactivity against the NS2 specific ORF. An antibody prepared against the NS2 specific ORF detected a protein of the correct size indicating that NS2 is a bona fide gene product in permissively infected cells. Consequently, NS2 may not be expressed in vivo during ADV infection. This finding might implicate disordered NS2 synthesis in restricted in vivo infection.