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Potential for transmission of sporadic Creutzfeldt–Jakob disease through peripheral routes

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Abstract

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.

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Fig. 1: Western blot analysis of protease-resistant PrPSc in the spleens of Ki-Hu129M/M or Ki-Hu129V/V mice intraperitoneally inoculated with sCJD isolates.

Data availability

The data that support the findings are available from the corresponding author upon request.

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Acknowledgements

We thank members of the Creutzfeldt–Jakob Disease Surveillance Committee in Japan, Creutzfeldt–Jakob disease specialists in the prefectures, and Creutzfeldt–Jakob disease patients and families for providing important clinical information. We thank Hiroko Kudo, Miyuki Yamamoto, and Ayumi Yamazaki for their excellent technical assistance.

Funding

This study was supported by JSPS KAKENHI Grant Number 18K05963 (AK), a grant from The Kato Memorial Trust for Nambyo Research (AK), The Kurata Grants from The Hitachi Global Foundation (AK), and a grant from Takeda Science Foundation (AK).

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Contributions

Conceptualization: AK and T Kitamoto; Methodology: SM and T Kitamoto; Formal analysis and investigation: AK, YM, and TS; Writing—original draft preparation: AK; Writing—review and editing: KA, T Kimura, SM, T Kitamoto; Funding acquisition: AK; Resources: T Kitamoto, SM; Supervision: T Kimura, SM, and T Kitamoto.

Corresponding author

Correspondence to Atsushi Kobayashi.

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Competing interests

The authors declare no competing interests.

Ethical approval

This study was approved by the Institutional Ethics Committee of Hokkaido University Faculty of Veterinary Medicine (approval number: VET1-5) and the Institutional Animal Care and Use Committees of Hokkaido University (approval number: 19-0025). All experiments using human materials are in compliance with the Helsinki Declaration. Animal experiments were performed in strict accordance with the Regulations for Animal Experiments and Related Activities at Hokkaido University.

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Kobayashi, A., Munesue, Y., Shimazaki, T. et al. Potential for transmission of sporadic Creutzfeldt–Jakob disease through peripheral routes. Lab Invest (2021). https://doi.org/10.1038/s41374-021-00641-2

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