Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University Prion Research Center, Fort Collins, Colorado 80523, USA.
Int Immunol. 2013 Dec;25(12):697-702. doi: 10.1093/intimm/dxt034. Epub 2013 Sep 13.
Accumulating evidence shows a critical role of the complement system in facilitating attachment of prions to both B cells and follicular dendritic cells and assisting in prion replication. Complement activation intensifies disease in prion-infected animals, and elimination of complement components inhibits prion accumulation, replication and pathogenesis. Chronic wasting disease (CWD) is a highly infectious prion disease of captive and free-ranging cervid populations that utilizes the complement system for efficient peripheral prion replication and most likely efficient horizontal transmission. Here we show that complete genetic or transient pharmacological depletion of C3 prolongs incubation times and significantly delays splenic accumulation in a CWD transgenic mouse model. Using a semi-quantitative prion amplification scoring system we show that C3 impacts disease progression in the early stages of disease by slowing the rate of prion accumulation and/or replication. The delayed kinetics in prion replication correlate with delayed disease kinetics in mice deficient in C3. Taken together, these data support a critical role of C3 in peripheral CWD prion pathogenesis.
越来越多的证据表明，补体系统在促进朊病毒附着到 B 细胞和滤泡树突状细胞以及辅助朊病毒复制方面起着关键作用。补体的激活会加剧感染朊病毒动物的疾病，而消除补体成分则会抑制朊病毒的积累、复制和发病机制。慢性消耗性疾病（CWD）是一种具有高度传染性的鹿科动物朊病毒病，它利用补体系统来有效地进行外周朊病毒复制，并且很可能有效地进行水平传播。在这里，我们表明，C3 的完全遗传或短暂的药理学耗竭可延长潜伏期，并显著延迟 CWD 转基因小鼠模型中脾脏的积累。使用半定量朊病毒扩增评分系统，我们表明 C3 通过减缓朊病毒积累和/或复制的速度来影响疾病的早期进展。朊病毒复制的延迟动力学与 C3 缺陷小鼠中疾病的延迟动力学相关。总之，这些数据支持 C3 在 CWD 朊病毒发病机制中的关键作用。
