Entry versus blockade of brain infection following oral or intraperitoneal scrapie administration: Role of prion protein expression in peripheral nerves and spleen
Entry versus blockade of brain infection following oral or intraperitoneal scrapie administration: Role of prion protein expression in peripheral nerves and spleen
复制标题
DOI：
10.1128/jvi.74.2.828-833.2000
复制
发表时间：
2000-01-01
影响因子：
5.4
通讯作者：
Chesebro, B
中科院分区：
文献类型：
--
作者：
Race, R;Oldstone, M;Chesebro, B
自然发生的传染性海绵状脑病（TSE）疾病，如牛的牛海绵状脑病，可能通过口腔或其他外周感染途径传播。虽然朊病毒蛋白（PrP）是易感性所必需的，但感染扩散到大脑的机制尚不清楚。两个突出的可能性包括通过白细胞的血源性传播和通过轴突运输的神经传播。在本实验中，口服或腹膜内感染转基因小鼠与仓鼠瘙痒症菌株263 K，仓鼠PrP在外周神经中的表达是足够的成功感染的大脑，和脾细胞不需要作为一个网站的扩增或作为运输的感染性。在这些转基因小鼠中，还研究了组织特异性PrP表达的外源PrP在干扰羊瘙痒病感染中的作用。异源PrP的外周表达完全保护了大多数小鼠在口服或腹腔内感染瘙痒症后免于临床疾病。在早期的干扰研究中没有看到这种广泛的保护作用，这些结果表明，突变PrP的基因治疗可能有效地预防TSE疾病。
Naturally occurring transmissible spongiform encephalopathy (TSE) diseases such as bovine spongiform encephalopathy in cattle are probably transmitted by oral or other peripheral routes of infection. While prion protein (PrP) is required for susceptibility, the mechanism of spread of infection to the brain is not clear. Two prominent possibilities include hematogenous spread by leukocytes and neural spread by axonal transport. In the present experiments, following oral or intraperitoneal infection of transgenic mice with hamster scrapie strain 263K, hamster PrP expression in peripheral nerves was sufficient for successful infection of the brain, and cells of the spleen were not required either as a site of amplification or as transporters of infectivity. The role of tissue-specific PrP expression of foreign PrP in interference with scrapie infection was also studied in these transgenic mice. Peripheral expression of heterologous PrP completely protected the majority of mice from clinical disease after oral or intraperitoneal scrapie infection. Such extensive protection has not been seen in earlier studies on interference, and these results suggested that gene therapy with mutant PrP may be effective in preventing TSE diseases.