Protein Misfolding Cyclic Amplification Cross-Species Products of Mouse-Adapted Scrapie Strain 139A and Hamster-Adapted Scrapie Strain 263K with Brain and Muscle Tissues of Opposite Animals Generate Infectious Prions.
Transmission of prions between mammalian species is limited by a "species barrier," a biological effect involving an increase in incubation period to decrease the percentage of animals succumbing to disease. In this study, we used protein misfolding cyclic amplification (PMCA) technique, which accelerates the conversion of prion proteins in vitro. Direct interspecies PMCA involving 144 cycles confirmed that both mouse-adapted scrapie strain 139A and hamster-adapted 263K could use brain homogenates of opposite species to form proteinase K (PK)-resistant PrP proteins (PrPres). Newly formed interspecies prions could stably propagate themselves in subsequent serial PMCA passages. The two types of PMCA-generated cross-species PrPreschanged their glycosylation profiles, which was similar to that observed during interspecies infection by the mouse agent 139A in vivo. These profiles were distinct from individual seeded PrPScand possessed properties of new hosts. Comparative analysis with respect to PK resistance showed no significant diversity between PMCA-PrPresand native PrPScor between brain and muscle PrPres. However, PrPresfrom the relatively early cycles of serial PMCA showed lower PK resistance than those from later cycles. Inoculation of these PMCA products amplified with homogeneous or heterogeneous brain tissues (cross-species products) induced experimental transmissible spongiform encephalopathies. These results suggested that PMCA can help prion strains to overcome species barrier and to propagate efficiently both in vitro and in vivo.
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.
Chen
C
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.
Jun
J
Han
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.|Shandong International Travel Healthcare Center, Shandong Entry-Exit Inspection and Quarantine Bureau, Qingdao, 266001, China.
Jin
J
Zhang
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
J
Wei
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.
Bao-Yun
BY
Zhang
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.
Chan
C
Tian
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.
Jie
J
Zhang
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
Q
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. dongxp238@sina.com.|Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. dongxp238@sina.com.
Xiao-Ping
XP
Dong
D000818:Animals; D001921:Brain / Q000473:pathology*; D006224:Cricetinae; D019286:Endopeptidase K / Q000378:metabolism; D006031:Glycosylation; D008297:Male; D051379:Mice; D009132:Muscles / Q000473:pathology*; D018620:PrPSc Proteins / Q000378:metabolism*; D017510:Protein Folding; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology*; D013045:Species Specificity
D018620:PrPSc Proteins; D019286:Endopeptidase K
Glycosylation; Prion; Protein misfolding cyclic amplification (PMCA); Species barrier; Strain; Transmissible spongiform encephalopathies (TSEs)