Tissue distribution of bovine spongiform encephalopathy agent in primates after intravenous or oral infection
Tissue distribution of bovine spongiform encephalopathy agent in primates after intravenous or oral infection
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DOI：
10.1016/s0140-6736(04)15487-1
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发表时间：
2004-02-07
期刊：
影响因子：
168.9
通讯作者：
Lasmézas, CI
中科院分区：
文献类型：
--
作者：
Herzog, C;Salès, N;Lasmézas, CI
背景 变异型克雅氏病 (vCJD) 患者的淋巴网状组织中存在与疾病相关的朊病毒蛋白 (Prp(res))。因此，该疾病可以通过手术或使用血液制品进行医源性传播。我们的目的是评估牛海绵状脑病 (BSE) 病原体通过静脉途径传播给灵长类动物的可能性，并研究其与口服途径感染相比的组织分布。 方法 通过静脉或口服方式，用第一代 BSE 动物的脑匀浆感染食蟹猴。对它们进行临床监测，观察神经系统症状的发生，并在疾病末期将它们人道处死。获取脑、淋巴网状组织、消化道和周围神经组织，通过夹心 ELISA 和免疫组织化学分析，定量和定性评估其 Prp(res) 含量。结果 BSE 静脉传播后的潜伏期比口腔感染后的潜伏期短得多。我们注意到 Prp(res) 存在于脾脏和扁桃体等淋巴网状组织以及从十二指肠到直肠的整个肠道中。在肠道中，PrPres 存在于派尔氏淋巴结、肠神经系统和肠粘膜神经纤维中。此外，在运动周围神经和自主神经系统中也发现了Prp(res)。 PrPres 的量范围为大脑中记录的量的 0.02% 到 10% 以上。通过静脉或口服途径感染的动物中 Prp(res) 的分布相似。 解释 我们的研究结果表明，与内窥镜手术相关的 vCJD 的可能风险目前可能被低估。静脉注射感染的人类医源性 vCJD 病例引起了与原发病例相同的公共卫生问题，并且需要在血液和组织捐献以及外科手术方面采取相同的预防措施。
Background The disease-associated form of prion protein (Prp(res)) has been noted in lymphoreticular tissues in patients with variant Creutzfeldt-Jakob disease (vCJD). Thus, the disease could be transmitted iatrogenically by surgery or use of blood products. We aimed to assess transmissibility of the bovine spongiform encephalopathy (BSE) agent to primates by the intravenous route and study its tissue distribution compared with infection by the oral route.Methods Cynomolgus macaques were infected either intravenously or orally with brain homogenates from first-passage animals with BSE. They were clinically monitored for occurrence of neurological signs and killed humanely at the terminal stage of the disease. Brain, lymphoreticular tissues, digestive tract, and peripheral nerves were obtained and analysed by sandwich ELISA and immunohistochemistry for quantitative and qualitative assessment of their Prp(res) content.Findings Incubation periods after intravenous transmission of BSE were much shorter than after oral infection. We noted that Prp(res) was present in lymphoreticular tissues such as spleen and tonsils and in the entire gut from the duodenum to the rectum. In the gut, PrPres was present in Peyer's patches and in the enteric nervous system and nerve fibres of intestinal mucosa. Furthermore, Prp(res) was found in locomotor peripheral nerves and the autonomic nervous system. Amount of PrPres ranged from 0.02% to more than 10% of that recorded in brain. Distribution of Prp(res) was similar in animals infected by the intravenous or oral route.Interpretation Our findings suggest that the possible risk of vCJD linked to endoscopic procedures might be currently underestimated. Human iatrogenic vCJD cases infected intravenously raise the same public-health concerns as primary cases and need the same precautionary measures with respect to blood and tissue donations and surgical procedures.