Journal of Biological Chemistry · 2007 · 70 citations · 28 references
Veterinary MedicineGeneticsMolecular GeneticsMedical GeneticsNeurogeneticsPrion DiseasesCreutzfeldt-jakob DiseaseFamilial Prion DiseaseGenetic DisordersNeurodegenerative DisordersNeuropathology Of Prion DiseasePrion Protein MisfoldingCodon 129 PolymorphismCreutzfeldt-jakob Disease PathologyDura MaterPolymorphisms At Codon 129Prion Disease Phenotype CorrelationPrion PathogenesisPrion Protein StrainsTransmissibility
The genotype (methionine or valine) at polymorphic codon 129 of the human prion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoform of PrP (PrPSc) are major determinants of the clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found that the transmission of sCJD prions from a patient with valine homozygosity (129V/V) and type 2 PrPSc (sCJD-VV2 prions) to mice expressing human PrP with methionine homozygosity (129M/M) generated unusual PrPSc intermediate in size between type 1 and type 2. The intermediate type PrPSc was seen in all examined dura mater graft-associated CJD cases with 129M/M and plaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prions exhibited similar transmissibility and neuropathology, and the identical type of PrPSc when inoculated into PrP-humanized mice with 129M/M or 129V/V. These findings suggest that p-dCJD could be caused by cross-sequence transmission of sCJD-VV2 prions. The genotype (methionine or valine) at polymorphic codon 129 of the human prion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoform of PrP (PrPSc) are major determinants of the clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found that the transmission of sCJD prions from a patient with valine homozygosity (129V/V) and type 2 PrPSc (sCJD-VV2 prions) to mice expressing human PrP with methionine homozygosity (129M/M) generated unusual PrPSc intermediate in size between type 1 and type 2. The intermediate type PrPSc was seen in all examined dura mater graft-associated CJD cases with 129M/M and plaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prions exhibited similar transmissibility and neuropathology, and the identical type of PrPSc when inoculated into PrP-humanized mice with 129M/M or 129V/V. These findings suggest that p-dCJD could be caused by cross-sequence transmission of sCJD-VV2 prions. Creutzfeldt-Jakob disease (CJD), 2The abbreviations used are: PrP, prion protein; PrPC, normal cellular isoform of PrP; PrPSc, abnormal isoform of PrP; PrPres, proteinase K-resistant core of PrPSc; 129M/M, methionine homozygosity at codon 129 of the human PrP gene; 129V/V, valine homozygosity at codon 129 of the human PrP gene; CJD, Creutzfeldt-Jakob disease; sCJD, sporadic CJD; p-dCJD, plaque-type dura mater graft-associated CJD; np-dCJD, non-plaque type dura mater graft-associated CJD; vCJD, variant CJD; dCJD, dura mater graft-associated CJD. kuru, scrapie, and bovine spongiform encephalopathy are lethal transmissible neurodegenerative diseases caused by an abnormal isoform of prion protein (PrPSc), which is converted from the normal cellular isoform (PrPC) (1Prusiner S.B. Scott M.R. DeArmond J.P. Cohen F.E. Cell. 1998; 93: 337-348Abstract Full Text Full Text PDF PubMed Scopus (831) Google Scholar). The genotype (methionine or valine) at polymorphic codon 129 of the human prion protein (PrP) gene and the type (type 1 or type 2) of PrPSc in the brain are major determinants of the clinicopathological phenotypes of sporadic CJD (sCJD) (2Parchi P. Castellani R. Capellari S. Ghetti B. Young K. Chen S.G. Farlow M. Dickson D.W. Sima A.A.F. Trojanowski J.Q. Petersen R.B. Gambetti P. Ann. Neurol. 1996; 39: 767-778Crossref PubMed Scopus (727) Google Scholar, 3Parchi P. Zou W. Wang W. Brown P. Capellari S. Ghetti B. Kopp N. Schulz-Schaeffer W.J. Kretzschmar H.A. Head M.W. Ironside J.W. Gambetti P. Chen S.G. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 10168-10172Crossref PubMed Scopus (268) Google Scholar, 4Parchi P. Capellari S. Chen S.G. Petersen R.B. Gambetti P. Kopp N. Brown P. Kitamoto T. Tateishi J. Giese A. Kretzschmar H. Nature. 1997; 386: 232-234Crossref PubMed Scopus (230) Google Scholar, 5Parchi P. Giese A. Capellari S. Brown P. Schulz-Schaeffer W. Windl O. Zerr I. Budka H. Kopp N. Piccardo P. Poser S. Rojiani A. Streichemberger N. Julien J. Vital C. Ghetti B. Gambetti P. Kretzschmar H. Ann. Neurol. 1999; 46: 224-233Crossref PubMed Scopus (1220) Google Scholar). Type 1 and type 2 PrPSc are distinguishable according to the size of the proteinase K-resistant core of PrPSc (PrPres) (21 and 19 kDa, respectively), reflecting differences in the proteinase K cleavage site (at residues 82 and 97, respectively) (2Parchi P. Castellani R. Capellari S. Ghetti B. Young K. Chen S.G. Farlow M. Dickson D.W. Sima A.A.F. Trojanowski J.Q. Petersen R.B. Gambetti P. Ann. Neurol. 1996; 39: 767-778Crossref PubMed Scopus (727) Google Scholar, 3Parchi P. Zou W. Wang W. Brown P. Capellari S. Ghetti B. Kopp N. Schulz-Schaeffer W.J. Kretzschmar H.A. Head M.W. Ironside J.W. Gambetti P. Chen S.G. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 10168-10172Crossref PubMed Scopus (268) Google Scholar). The genotype at codon 129 also influences the susceptibility to variant CJD (vCJD), iatrogenic CJD, and kuru (6Zeidler M. Stewart G. Cousens S.N. Estibeiro K. Will R.G. Lancet. 1997; 350: 668Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 7Wadsworth J.D.F. Asante E.A. Desbruslais M. Linehan J.M. Joiner S. Gowland I. Welch J. Stone L. Lloyd S.E. Hill A.F. Brandner S. Collinge J. Science. 2004; 306: 1793-1796Crossref PubMed Scopus (227) Google Scholar, 8Asano M. Mohri S. Ironside J.W. Ito M. Tamaoki N. Kitamoto T. Biochem. Biophys. Res. Commun. 2006; 342: 293-299Crossref PubMed Scopus (46) Google Scholar, 9Collinge J. Palmer M.S. Dryden A.J. Lancet. 1991; 337: 1441-1442Abstract PubMed Scopus (482) Google Scholar, 10Deslys J.P. Marce D. Dormont D. J. Gen. Virol. 1994; 75: 23-27Crossref PubMed Scopus (101) Google Scholar, 11Lee H.S. Brown P. Cervenáková L. Garruto R.M. Alpers M.P. Gajdusek D.C. Goldfarb L.G. J. Infect. Dis. 2001; 183: 192-196Crossref PubMed Scopus (128) Google Scholar). A transmission study using transgenic mice expressing human PrP revealed that the congruency of the genotype at codon 129 between the inoculum and the inoculated transgenic mice determines the susceptibility to sCJD prions (12Korth C. Kaneko K. Groth D. Heye N. Telling G. Mastrianni J. Parchi P. Gambetti P. Will R. Ironside J. Heinrich C. Tremblay P. DeArmond S.J. Prusiner S.B. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 4784-4789Crossref PubMed Scopus (111) Google Scholar). Transmission of sCJD prions to mice with an incongruent genotype (referred to as cross-sequence transmission) results in a relatively long incubation period. The potential for cross-sequence transmission should be considered in the iatrogenic transmission of CJD via cadaveric pituitary hormones, dura mater and corneal grafts, or contaminated neurosurgical instruments. More than half of the reported cases of dura mater graft-associated CJD (dCJD) occurred in Japan, where 123 cases have been recognized as of February 2006 (13Brown P. Preece M. Brandel J.P. Sato T. McShane L. Zerr I. Fletcher A. Will R.G. Pocchiari M. Cashman N.R. d'Aignaux J.H. Cervenáková L. Fradkin J. Schonberger L.B. Collins S.J. Neurology. 2000; 55: 1075-1081Crossref PubMed Scopus (469) Google Scholar, 14Hoshi K. Yoshino H. Urata J. Nakamura Y. Yanagawa H. Sato T. Neurology. 2000; 55: 718-721Crossref PubMed Scopus (59) Google Scholar, 15Nakamura Y. Watanabe M. Nagoshi K. Kitamoto T. Sato T. Yamada M. Mizusawa H. Maddox R. Sejvar J. Belay E. Schonberger L.B. MMWR. Morb. Mortal. Wkly. Rep. 2003; 52: 1179-1181PubMed Google Scholar, 16Brown P. Brandel J.P. Preese M. Sato T. Neurology. 2006; 67: 389-393Crossref PubMed Scopus (175) Google Scholar). The dural grafts used in Japan were manufactured by German companies (13Brown P. Preece M. Brandel J.P. Sato T. McShane L. Zerr I. Fletcher A. Will R.G. Pocchiari M. Cashman N.R. d'Aignaux J.H. Cervenáková L. Fradkin J. Schonberger L.B. Collins S.J. Neurology. 2000; 55: 1075-1081Crossref PubMed Scopus (469) Google Scholar, 14Hoshi K. Yoshino H. Urata J. Nakamura Y. Yanagawa H. Sato T. Neurology. 2000; 55: 718-721Crossref PubMed Scopus (59) Google Scholar, 15Nakamura Y. Watanabe M. Nagoshi K. Kitamoto T. Sato T. Yamada M. Mizusawa H. Maddox R. Sejvar J. Belay E. Schonberger L.B. MMWR. Morb. Mortal. Wkly. Rep. 2003; 52: 1179-1181PubMed Google Scholar). In Europe, 28.4% of sCJD patients are valine homozygotes (129V/V) or methionine/valine heterozygotes at codon 129 (129M/V) (5Parchi P. Giese A. Capellari S. Brown P. Schulz-Schaeffer W. Windl O. Zerr I. Budka H. Kopp N. Piccardo P. Poser S. Rojiani A. Streichemberger N. Julien J. Vital C. Ghetti B. Gambetti P. Kretzschmar H. Ann. Neurol. 1999; 46: 224-233Crossref PubMed Scopus (1220) Google Scholar). 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Kitamoto T. J. Gen. Virol. 2003; 84: 2885-2893Crossref PubMed Scopus (49) Google Scholar). The for the of two distinct phenotypes in dCJD the of p-dCJD, we inoculated sCJD prions into mice expressing human PrP with 129M/M or 129V/V. Here we that cross-sequence transmission of sCJD prions from a patient with and type 2 PrPSc (sCJD-VV2 prions) caused phenotypes similar to those of of and of mice expressing human PrP with 129M/M and mice been reported M. Mohri S. Ironside J.W. Ito M. Tamaoki N. Kitamoto T. Biochem. Biophys. Res. Commun. 2006; 342: 293-299Crossref PubMed Scopus (46) Google Scholar). mice expressing human PrP with 129M/M and transgenic mice expressing human PrP with and and mice were generated as T. Nakamura K. K. S. Y. M. Tateishi J. Biochem. Biophys. Res. Commun. 1996; PubMed Scopus Google Scholar, T. Mohri S. Ironside J.W. I. Tanaka T. Kitamoto N. S. N. M. J. Muramoto T. Biochem. Biophys. Res. Commun. PubMed Scopus Google Scholar). the of of the PrP and mice were with or mice M. Mohri S. Ironside J.W. Ito M. Tamaoki N. Kitamoto T. Biochem. Biophys. Res. Commun. 2006; 342: 293-299Crossref PubMed Scopus (46) Google Scholar). The of human PrP in the from and mice were and the in or Brain were at from CJD patients after for The of CJD and the type of PrPSc were by PrPSc and as T. K. N. M. Muramoto T. Tateishi J. J. Pathol. Google Scholar, Y. Mohri S. Ironside J.W. Muramoto T. Kitamoto T. J. Pathol. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). The genotype and the absence of in the of the PrP gene were by T. M. K. S. Y. Tateishi J. Biochem. Biophys. Res. Commun. PubMed Scopus Google Scholar). Transmission brain and brain were as T. Mohri S. Ironside J.W. I. Tanaka T. Kitamoto N. S. N. M. J. Muramoto T. Biochem. Biophys. Res. Commun. PubMed Scopus Google Scholar). Transmission were using of the for or for M. Mohri S. Ironside J.W. Ito M. Tamaoki N. Kitamoto T. Biochem. Biophys. Res. Commun. 2006; 342: 293-299Crossref PubMed Scopus (46) Google Scholar, Y. Mohri S. Ironside J.W. Muramoto T. Kitamoto T. J. Pathol. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). inoculated mice were after the of and were or in inoculated mice were at and were or and were with for 1 to the and in were by PrP T. K. N. M. Muramoto T. Tateishi J. J. Pathol. Google Scholar). The was used as the T. Muramoto T. C. K. Tateishi J. Brain Res. 1991; PubMed Scopus Google Scholar). with the were used as the was from human or and with as M. N. M. Arch. Virol. 1996; PubMed Scopus (44) Google with of PrP, were with were to and as M. Mohri S. Ironside J.W. Ito M. Tamaoki N. Kitamoto T. Biochem. Biophys. Res. Commun. 2006; 342: 293-299Crossref PubMed Scopus (46) Google Scholar). The and the M. Mohri S. Ironside J.W. Ito M. Tamaoki N. Kitamoto T. Biochem. Biophys. Res. Commun. 2006; 342: 293-299Crossref PubMed Scopus (46) Google were used as the and were used as the are as S.E. Transmission of sCJD to PrP-humanized with 129M/M or of sCJD prions be cross-sequence we of a brain from a patient or that from a sCJD-VV2 patient into PrP mice with the 129M/M or the incubation of mice were and of of inoculated which were than those of mice sCJD-VV2 the incubation of mice was which was than that of mice PrP deposits in the from and mice inoculated with prions In contrast, mice inoculated with sCJD-VV2 prions plaque-type PrP deposits in the and to deposits in the The plaque-type PrP deposits were in the from mice inoculated with sCJD-VV2 in which plaque-type PrP deposits the and than the revealed that the size of in the was after cross-sequence transmission of prions sCJD-VV2 prions and mice inoculated with prions type 1 as of generated which were identical in size to from mice inoculated with sCJD-VV2 prions unusual that were than from mice than or as with an size from the inoculated type 2 The in the size of and the in mice that the of sCJD-VV2 prions were cross-sequence of sCJD prions to mice with 129M/M or of human PrP in the S.E. of of inoculated of than prion The of human PrP in the of of inoculated of than prion in a Type in p-dCJD mice inoculated with sCJD-VV2 prions plaque-type PrP deposits in the 129M/M CJD patients with the 129M/M genotype and plaque-type PrP deposits have been recognized in and we have classified cases into and p-dCJD cases into there been an of p-dCJD that the of intermediate in size between type 1 and type 2 H.A. Sethi S. Földvári Z. Windl O. Querner V. Zerr I. Poser S. Brain Pathol. 2003; 13: 245-249Crossref PubMed Scopus (40) Google Scholar). The occurrence of plaque-type PrP deposits and in mice inoculated with sCJD-VV2 prions the possibility that p-dCJD could be caused by cross-sequence transmission of sCJD-VV2 prions. we the size of in the from p-dCJD that the size of from p-dCJD cases was than that of from or np-dCJD cases A and that the intermediate type reported by Kretzschmar and H.A. Sethi S. Földvári Z. Windl O. Querner V. Zerr I. Poser S. Brain Pathol. 2003; 13: 245-249Crossref PubMed Scopus (40) Google is a in human p-dCJD intermediate type in p-dCJD cases as Transmission of p-dCJD to PrP-humanized with 129M/M or the transmissibility of p-dCJD we of brain from p-dCJD patients into PrP-humanized mice with the 129M/M or mice expressing human PrP with 129M/M and we mice expressing human PrP with The or of human PrP are with CJD M.S. Hill A.F. Laplanche J.L. Collinge J. PubMed Scopus Google Scholar). mice long incubation of in were with mice to the human PrP mice were to prions we used as PrP-humanized mice with the 129M/M genotype in at of and mice inoculated with p-dCJD prions disease The incubation of mice were and the of human PrP in mice was than that of the incubation of mice were than those of mice and np-dCJD, the incubation of mice were and 2 of the from mice inoculated with p-dCJD prions a plaque-type PrP deposits similar to those in mice inoculated with sCJD-VV2 prions mice inoculated with p-dCJD prions plaque-type PrP deposits in the and to deposits in the similar to those in mice inoculated with sCJD-VV2 prions. was plaque-type PrP deposits in the from mice inoculated with np-dCJD prions revealed that mice inoculated with p-dCJD prions the intermediate type which were identical in size to and mice inoculated with p-dCJD prions type 2 which were identical in size to p-dCJD prions and sCJD-VV2 prions were similar in the the of PrP and the size of intermediate type in or type 2 in in PrP-humanized of p-dCJD prions or sCJD-VV2 prions to mice with 129M/M or S.E. of of inoculated of of inoculated in a the of the we considered that the of of PrP the size of mice inoculated with prions identical in size to from mice mice inoculated with sCJD-VV2 prions identical in size to from mice inoculated a brain from a p-dCJD patient into mice The incubation of mice was These mice identical in size to from mice Transmission of p-dCJD or sCJD-VV2 to PrP-humanized with 129M/M or the in the transmissibility between p-dCJD prions and sCJD-VV2 we of the brain from a p-dCJD patient or that from a sCJD-VV2 patient into PrP-humanized mice as T. Mohri S. Ironside J.W. I. Tanaka T. Kitamoto N. S. N. M. J. Muramoto T. Biochem. Biophys. Res. Commun. PubMed Scopus Google Scholar). of the at revealed that mice were to p-dCJD prions than mice mice were to sCJD-VV2 prions than In contrast, mice inoculated with prions PrP in the we that p-dCJD prions and sCJD-VV2 prions exhibited similar transmissibility to PrP-humanized mice in In mice inoculated with sCJD-VV2 prions in the Meanwhile, mice inoculated with sCJD-VV2 prions we the of the size also in the cross-sequence transmission of sCJD-VV2 prions to mice caused phenotypes similar to those of p-dCJD, we also examined the transmissibility of sCJD-VV2 prions as of the brain from a that to sCJD-VV2 prions into PrP-humanized of mice inoculated with prions PrP in the cross-sequence of the revealed that mice type identical in size to Meanwhile, mice type 2 identical in size to data of major transmission of sCJD-VV2 prions to mice generated unusual intermediate in size between type 1 and type 2. the intermediate type was seen in all examined p-dCJD mice inoculated with p-dCJD prions incubation and the of type 2 with a size from the intermediate type mice inoculated with prions high susceptibility and the of type 2 with a size from type These findings suggest that p-dCJD could be caused by transmission of sCJD-VV2 prions to with the 129M/M genotype results that p-dCJD prions and np-dCJD prions are distinct the intermediate type was found to be a in p-dCJD the features of p-dCJD the intermediate type PrPres, the long incubation and plaque-type PrP deposits in the brain were after transmission to PrP-humanized mice with Meanwhile, the mice with 129M/M inoculated with np-dCJD prions type 1 PrPres, a incubation and PrP deposits in the These results that p-dCJD and np-dCJD are distinct of caused by distinct prion The long incubation of the mice inoculated with p-dCJD prions suggest the possibility that the of p-dCJD patients in the sCJD cases with the genotype and type 2 PrPSc and sCJD-VV2 cases for of the sCJD cases and show the by plaque-type PrP deposits (5Parchi P. Giese A. Capellari S. Brown P. Schulz-Schaeffer W. Windl O. Zerr I. Budka H. Kopp N. Piccardo P. Poser S. Rojiani A. Streichemberger N. Julien J. Vital C. Ghetti B. Gambetti P. Kretzschmar H. Ann. Neurol. 1999; 46: 224-233Crossref PubMed Scopus (1220) Google Scholar). and p-dCJD have been in and transmission (18Shimizu S. Hoshi K. Muramoto T. Homma M. Ironside J.W. Kuzuhara S. Sato T. Yamamoto T. Kitamoto T. Arch. Neurol. 1999; 56: 357-362Crossref PubMed Scopus (79) Google Scholar, 19Mochizuki Y. Mizutani T. Tajiri N. Oinuma T. Nemoto N. Kakimi S. Kitamoto T. Neuropathology. 2003; 23: 136-140Crossref PubMed Scopus (14) Google Scholar, 20Kretzschmar H.A. Sethi S. Földvári Z. Windl O. Querner V. Zerr I. Poser S. Brain Pathol. 2003; 13: 245-249Crossref PubMed Scopus (40) Google Scholar, 21Satoh K. Muramoto T. Tanaka T. Kitamoto N. Ironside J.W. Nagashima K. Yamada M. Sato T. Mohri S. Kitamoto T. J. Gen. Virol. 2003; 84: 2885-2893Crossref PubMed Scopus (49) Google Scholar, Y. Mohri S. Ironside J.W. Muramoto T. Kitamoto T. J. Pathol. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). Although the results of the study show that cross-sequence transmission of sCJD-VV2 prions phenotypes similar to those of p-dCJD, are to prions a p-dCJD in mice with p-dCJD, a iatrogenic CJD cases with the 129M/M genotype and plaque-type PrP deposits in the brain have been reported in human CJD N. P. J. J.L. A. Neurol. Google Scholar, T. A. Deslys J.P. Dormont D. L. J. O. 1994; PubMed Scopus Google Scholar). The results to that the human CJD cases with 129M/M and plaque-type PrP deposits might be caused by the cross-sequence transmission of sCJD-VV2 prions. cross-sequence sCJD-VV2 prions as by the of the size of A similar of the size cross-sequence transmission been reported in mice inoculated with prions Y. Mohri S. Ironside J.W. Muramoto T. Kitamoto T. J. Pathol. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, A.F. Desbruslais M. Joiner S. Gowland I. Collinge J. Nature. 1997; PubMed Scopus Google or A.F. Joiner S. Linehan J. Desbruslais M. Collinge J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: PubMed Scopus Google Scholar, D. G. Y. J. DeArmond S.J. Prusiner S.B. Scott M.R. 34: Full Text Full Text PDF PubMed Scopus Google Scholar). the size of to those of transmission to A.F. Joiner S. Linehan J. Desbruslais M. Collinge J. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: PubMed Scopus Google Scholar). In with the intermediate type to type 2 when prions or p-dCJD prions were to the mice with in The for findings is that to the of a PrPSc from the population in the of a prion with and that the prion the of the prions PrPSc the prion is to the the prions and The is by the M. Mohri S. Ironside J.W. Ito M. Tamaoki N. Kitamoto T. Biochem. Biophys. Res. Commun. 2006; 342: 293-299Crossref PubMed Scopus (46) Google mice and transgenic mice expressing bovine PrP are to prions as as bovine spongiform encephalopathy prions M. Mohri S. Ironside J.W. Ito M. Tamaoki N. Kitamoto T. Biochem. Biophys. Res. Commun. 2006; 342: 293-299Crossref PubMed Scopus (46) Google Scholar, M.R. D. DeArmond S.J. Prusiner S.B. J. Virol. PubMed Scopus Google Scholar). with a using transgenic mice expressing human PrP with or (12Korth C. Kaneko K. Groth D. Heye N. Telling G. Mastrianni J. Parchi P. Gambetti P. Will R. Ironside J. Heinrich C. Tremblay P. DeArmond S.J. Prusiner S.B. Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 4784-4789Crossref PubMed Scopus (111) Google the mice with in study were to sCJD-VV2 prions than the mice with the mice with high susceptibility to prions and p-dCJD prions cross-sequence These be as prions and p-dCJD prions the of the sCJD-VV2 the mice with were to prions as as sCJD-VV2 prions. results that be a to the of prions. In the of prions were cross-sequence transmission The mice with type 1 after with prions. cases are (at of the of sCJD and characterized by at (5Parchi P. Giese A. Capellari S. Brown P. Schulz-Schaeffer W. Windl O. Zerr I. Budka H. Kopp N. Piccardo P. Poser S. Rojiani A. Streichemberger N. Julien J. Vital C. Ghetti B. Gambetti P. Kretzschmar H. Ann. Neurol. 1999; 46: 224-233Crossref PubMed Scopus (1220) Google results raise the possibility that CJD cases classified as cases caused by iatrogenic transmission of prions or by type 1 prions from disease prions in In fact, two patients or have been reported Gambetti P. Schonberger L.B. Parchi P. Capellari S. J.H. K. G. J.M. Arch. Neurol. 2001; PubMed Scopus Google Scholar, Maddox M.W. Gambetti P. Schonberger L.B. Infect. Dis. 2004; PubMed Scopus Google Scholar). The results of the study the for and of the of prions. In cross-sequence transmission of sCJD-VV2 prions a prion with and disease phenotypes as p-dCJD prions. the generated prions have unique transmissibility the In the prion cross-sequence from to the of the prions. H. and K. for and and B. for of the
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