PRNP sequences of Tibetan antelope, blue sheep and plateau pika from Qinghai-Tibet Plateau and the reactivities of their PrP proteins to rodent-adapted scrapie strains in RT-QuIC and PMCA

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Yue Zhang Wu# State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China

Jing-Xing Wu# State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China

Xue-Hua Yang State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China

Shan Lu State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China

Kang Xiao State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China

Dong-Dong Chen State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China

Li-Ping Gao State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China

Qi Shi* State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China++China Academy of Chinese Medical Sciences, Beijing 100700, China

Jian-Guo Xu* State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China

Xiao-Ping Dong* State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Zhejiang University), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, China++Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China++China Academy of Chinese Medical Sciences, Beijing 100700, China++Shanghai Institute of Infectious Disease and Biosafety, Shanghai, China

# contributed equally to this work


Abstract

Background: Tibetan antelope (Rhinopithecus), blue sheep (Pseudois nayauris) and plateau pika (Ochotona curzoniae) are wild animals living in Qinghai-Tibet Plateau. Up to now, there is no report of naturally occurred TSE upon these animals. Their PRNP genes are not described in literature. 

Methods: We obtained and sequenced the PRNP genes from 21 Tibetan antelopes, 4 blue sheep and 3 plateau pikas. Then we prepared their recombinant proteins. Using scrapie strains 263K, 139A, ME7 and S15 as the seeds, we tested the reactivities of the PrP proteins from sheep (rSheepPrP25-234) and pika (rPikaPrP23-230) in RT-QuIC. We also did the PMCA tests of the brain homogenates of domestic sheep and rabbit with the seeds of strains 263K and ME7. 

Results: The PRNP genes of bovids were 771 bp long and encoded 256 amino acids (aa.), showing 100% homology with wild-type sheep PrP aa. sequence. The PRNP gene of pika was 759 bp long and encoded 252 amino acids, showing 92.1% homology with aa. sequence of domestic rabbit. Both the proteins of sheep and pika revealed positive reactions in 10-5 diluted seeds. Only rPikaPrP23-230 produced positive curves in 10-7 diluted seeds. PMCA tests ailed to produce PK-resistant PrP (PrPres). 

Conclusion: It is the first description of PRNP genes and PrP aa. sequences of those three animals in Qinghai-Tibet Plateau. In the presences of rodent prions, the PrPs of sheep and pika efficiently form fibrillation in RT-QuIC, but do not generate PrPres in PMCA. Our results indicate that pika, as one of the important links in the biological chain in Qinghai-Tibet Plateau, may play an important role in prion circulation. And pika PrP deserves further analysis for its potential application value in the assays for human prion disease.

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Bioinformatics, Genomics
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  • 06 Jan 2023 08:52 Version 1
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