Complement protein C3 exacerbates prion disease in a mouse model of chronic wasting disease.
Complement protein C3 exacerbates prion disease in a mouse model of chronic wasting disease.
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DOI：
10.1093/intimm/dxt034
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发表时间：
2013-12
影响因子：
4.4
通讯作者：
Brady A. Michel;Adam Ferguson;Theodore Johnson;Heather R. Bender;Crystal Meyerett-Reid;A. Wyckoff;B. Pulford;G. Telling;M. Zabel
中科院分区：
文献类型：
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作者：
Brady A. Michel;Adam Ferguson;Theodore Johnson;Heather R. Bender;Crystal Meyerett-Reid;A. Wyckoff;B. Pulford;G. Telling;M. Zabel
越来越多的证据表明，补体系统在促进朊病毒附着于B细胞和滤泡树突细胞以及辅助朊病毒复制中起着关键作用。补体激活加剧朊病毒感染动物的疾病，消除补体成分抑制朊病毒的积累，复制和发病机制。慢性消耗性疾病（CWD）是一种高度传染性的朊病毒疾病的圈养和自由放养的鹿科种群，利用补体系统有效的外周朊病毒复制和最有可能有效的水平传播。在这里，我们表明，完全遗传或短暂的药理学消耗的C3的潜伏期，并显着延迟CWD转基因小鼠模型中的脾脏积累。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/或复制的速率在疾病的早期阶段影响疾病进展。朊病毒复制的延迟动力学与C3缺陷小鼠的延迟疾病动力学相关。总之，这些数据支持C3在外周慢性消耗病朊病毒发病机制中的关键作用。
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.