PATHOGENESIS OF ALEUTIAN MINK DISEASE PARVOVIRUS INFECTIONS

阿留申水貂病细小病毒感染的发病机制

• 批准号: 6431513
• 负责人: Marshall Elliott Bloom
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431513
• 关键词: Carnivora; Parvoviridae; antibody formation; antiviral antibody; capsid; communicable disease diagnosis; cytokine; host organism interaction; immunoelectrophoresis; laboratory rabbit; microorganism culture; microorganism immunology; nucleic acid sequence; pathologic process; polymerase chain reaction; virus antigen; virus protein

Persistent infection of adult mink with the Aleutian mink disease parvovirus (ADV)leads to disturbances of immune regulation, including hypergammaglobulinemia, plasmacytosis, immune complex disease, interstitial and glomerulonephritis. Infection at the cellular level is noncytopathic and restricted. In contrast, infections in cell culture and in newborn mink are cytopathic and fully permissive. Studies in cell culture, using TUNEL labeling and annexin staining, have revealed that cells engaged in permissive ADV infection replication become apoptotic. Pretreatment of cells with a broad-spectrum caspase inhibitor or a specific inhibitor of the executioner caspase 3, blocks permissive replication at a step prior to viral protein expression. Treatment with an inhibitor specific for caspase 6/8 produces a partial block. Thus, ADV induces programmed cell death (apoptosis) and is in fact dependent upon apoptosis for complete viral replication. Populations of native feral mustelids in Spain are declining. The presence of ADV infection has been documented in these animals. More than 1 sequence variant of ADV appears to be circulating and these variants differ from previously identified isolates of ADV.

成年水貂持续感染阿留申水貂病细小病毒（ADV）会导致免疫调节紊乱，包括高丙种球蛋白血症、浆细胞增多症、免疫复合物疾病、间质性肾炎和肾小球肾炎。细胞水平的感染是非细胞病变的且受到限制。相比之下，细胞培养物和新生水貂中的感染是细胞病变的并且是完全允许的。使用 TUNEL 标记和膜联蛋白染色进行的细胞培养研究表明，参与允许 ADV 感染复制的细胞会发生凋亡。用广谱 caspase 抑制剂或刽子手 caspase 3 的特异性抑制剂对细胞进行预处理，可在病毒蛋白表达之前的步骤中阻止允许的复制。使用 caspase 6/8 特异性抑制剂进行处理会产生部分阻断。因此，ADV 诱导程序性细胞死亡（细胞凋亡），并且实际上依赖于细胞凋亡来完成病毒复制。西班牙本土野生鼬科动物的数量正在下降。这些动物中已记录了 ADV 感染的存在。似乎有超过 1 种 ADV 序列变体正在传播，这些变体与之前发现的 ADV 分离株不同。