Potential for transmission of sporadic Creutzfeldt-Jakob disease through peripheral routes
Potential for transmission of sporadic Creutzfeldt-Jakob disease through peripheral routes
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DOI：
10.1038/s41374-021-00641-2
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发表时间：
2021-07-12
影响因子：
5
通讯作者：
Kitamoto, Tetsuyuki
中科院分区：
文献类型：
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作者：
Kobayashi, Atsushi;Munesue, Yoshiko;Kitamoto, Tetsuyuki
迄今为止，根据患者的临床病理特征、异常朊蛋白的生化特性和传播特性的差异，已确定了五种散发性克雅氏病（CJD）菌株。最近的进展，我们的知识医源性传播的散发性CJD提出了可能性，散发性CJD菌株通过外周途径的感染性是不同的颅内感染。为了测试这种可能性，在这里，我们首次使用表达人朊蛋白的小鼠模型系统地评估了散发性CJD菌株通过外周途径的感染性。虽然在脑内传播研究中，V2和M1散发性CJD毒株的感染性几乎相同，但V2毒株通过外周途径感染的效率高于M1毒株。其他散发的CJD菌株缺乏传染性。值得注意的是，V2和M1品系都显示出对PRNP多态性密码子处具有缬氨酸纯合性的小鼠的偏好。这些结果表明，V2株是通过外周途径感染的最具传染性的散发性CJD株。此外，这些研究结果提出了这样的可能性，即与蛋氨酸纯合子相比，在PRNP多态性密码子处具有缬氨酸纯合性的个体通过外周途径感染的风险可能更高。因此，预防V2散发性CJD株传播的措施对于根除医源性CJD通过外周途径传播将是重要的，作者试图确定散发性Creutzfeldt-Jakob病朊病毒株通过外周途径的感染性是否与颅内感染不同。他们发现，在这些菌株中，V2通过外周途径感染性最强。因此，针对该菌株传播的预防措施对于根除克雅氏病的医源性传播至关重要。
Five sporadic Creutzfeldt-Jakob disease (CJD) strains have been identified to date, based on differences in clinicopathological features of the patients, the biochemical properties of abnormal prion proteins, and transmission properties. Recent advances in our knowledge about iatrogenic transmission of sporadic CJD have raised the possibility that the infectivity of sporadic CJD strains through peripheral routes is different from that of intracranial infection. To test this possibility, here we assessed systematically the infectivity of sporadic CJD strains through the peripheral route for the first time using a mouse model expressing human prion protein. Although the infectivity of the V2 and M1 sporadic CJD strains is almost the same in intracerebral transmission studies, the V2 strain infected more efficiently than the M1 strain through the peripheral route. The other sporadic CJD strains examined lacked infectivity. Of note, both the V2 and M1 strains showed preference for mice with the valine homozygosity at the PRNP polymorphic codon. These results indicate that the V2 strain is the most infectious sporadic CJD strain for infection through peripheral routes. In addition, these findings raise the possibility that individuals with the valine homozygosity at the PRNP polymorphic codon might have higher risks of infection through peripheral routes compared with the methionine homozygotes. Thus, preventive measures against the transmission of the V2 sporadic CJD strain will be important for the eradication of iatrogenic CJD transmission through peripheral routes.The authors sought to determine whether the infectivity of sporadic Creutzfeldt-Jakob disease prion strains through peripheral routes is different from that from intracranial infection. They found that among the strains, V2 is the most infectious through peripheral routes. Thus, preventive measures against transmission of this strain will be important for the eradication of iatrogenic transmission of Creutzfeldt-Jakob disease.