Infectivity and host responses in Creutzfeldt-Jakob disease
Infectivity and host responses in Creutzfeldt-Jakob disease
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DOI：
10.1006/viro.1996.0033
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发表时间：
1996-02-01
期刊：
影响因子：
3.7
通讯作者：
Fritch, W
中科院分区：
文献类型：
--
作者：
Manuelidis, L;Fritch, W
评价了克雅氏病（CJD）中病毒滴度与宿主反应之间的关系。仓鼠脑中97%的病毒在5天内迅速清除，残留病毒均匀分散到两个半球。指数复制仅在类似于30天的长时间的蚀食期后开始，并且到100天时显示滴度增加>3个对数。然而，从100天到135天，滴度被限制在类似于10（8）/g的平台水平。相比之下，先前的研究表明，仓鼠瘙痒症没有明显的蚀相，脑滴度高于或等于100倍。我们的计算还揭示了克雅氏病的有效倍增时间（t（j））为7.6天，而痒病的t（j）明显不同，约为3天。因此，这些菌株中的每一种都编码不同的起始和复制程序。最相关的宿主分子反应包括54天的早期星形胶质细胞活性，不伴有形态或行为变化。宿主PrP的变化很小，直到87天滴度已经达到2 × 10（7）/g。在接下来的20天，60%的脑PrP成为有限的蛋白水解，但总PrP没有增加。这些爆发性PrP变化发生在病毒停滞和随后的海绵状变性之前。因为这些和其他数据是不一致的PrP本身是感染剂，我们讨论了一个模型，其中渐进的PrP和神经胶质细胞激活的一部分，最终的主机策略，包含一个病毒，是无害的低滴度。这种策略是有缺陷的，因为PrP是大脑中自我毁灭的独立杀手。然而，在外周，这种策略可能会消除罕见的感染细胞。(C)出版社：Academic Press，Inc.
The relationship between viral titer and host responses was evaluated in Creutzfeldt-Jakob Disease (CJD). Rapid clearing of 97% of the virus from hamster brain occurred within 5 days, and residual virus was dispersed equally to both hemispheres. Exponential replication began only after a long eclipse phase of similar to 30 days, and by 100 days showed an >3 log increase in titer. However, from 100 to 135 days, titers were restricted to plateau levels of similar to 10(8)/g. In comparison, previous studies show no appreciable eclipse phase and greater than or equal to 100-fold higher brain titers in hamster scrapie. Our calculations also revealed an effective doubling time (t(j)) of 7.6 days in CJD and a markedly different t(j) of similar to 3 days in scrapie. Thus different initiation and replication programs are encoded by each of these strains. The most pertinent host molecular responses included early astrocytic activity by 54 days, unaccompanied by morphological or behavioral changes. Changes in host PrP were minimal until 87 days when titers were already 2 x 10(7)/g. In the next 20 days 60% of brain PrP became resistant to limited proteolysis but total PrP did not increase. These fulminant PrP changes preceded viral arrest and subsequent spongiform degeneration. Because these and other data are not consistent with PrP itself being the infectious agent, we discuss a model in which progressive PrP and glial activation are part of a final host strategy to contain a virus that is innocuous at low titers. This strategy is flawed because PrP is an independent provocateur of self-destruction in the brain. However, in the periphery this strategy may eliminate rare infected cells. (C) 1996 Academic Press, Inc.