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Conversion of the BASE Prion Strain into the BSE Strain:

flounder

Well-known member
Conversion of the BASE Prion Strain into the BSE Strain: The Origin of BSE?

Raffaella Capobianco1, Cristina Casalone2, Silvia Suardi1, Michela Mangieri1, Claudia Miccolo1, Lucia Limido1,
Marcella Catania1, Giacomina Rossi1, Giuseppe Di Fede1, Giorgio Giaccone1, Maria Grazia Bruzzone1, Ludovico Minati1,
Cristiano Corona2, Pierluigi Acutis2, Daniela Gelmetti3, Guerino Lombardi3, Martin H. Groschup4, Anne Buschmann4,
Gianluigi Zanusso5, Salvatore Monaco5, Maria Caramelli2, Fabrizio Tagliavini1*
1 Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Milan, Italy, 2 Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Torino, Italy, 3 Istituto
Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Brescia, Italy, 4 Friedrich-Loeffler-Institut, Institute for Novel and Emerging Infectious Diseases, Greifswald,
Insel Riems, Germany, 5 Department of Neurological and Visual Science, Section of Clinical Neurology, Policlinico G. B. Rossi, Verona, Italy

Atypical neuropathological and molecular phenotypes of bovine spongiform encephalopathy (BSE) have recently been
identified in different countries. One of these phenotypes, named bovine ‘‘amyloidotic’’ spongiform encephalopathy
(BASE), differs from classical BSE for the occurrence of a distinct type of the disease-associated prion protein (PrP),
termed PrPSc, and the presence of PrP amyloid plaques. Here, we show that the agents responsible for BSE and BASE
possess different biological properties upon transmission to transgenic mice expressing bovine PrP and inbred lines of
nontransgenic mice. Strikingly, serial passages of the BASE strain to nontransgenic mice induced a neuropathological
and molecular disease phenotype indistinguishable from that of BSE-infected mice. The existence of more than one
agent associated with prion disease in cattle and the ability of the BASE strain to convert into the BSE strain may have
important implications with respect to the origin of BSE and spongiform encephalopathies in other species, including
humans.

Citation: Capobianco R, Casalone C, Suardi S, Mangieri M, Miccolo C, et al. (2007) Conversion of the BASE prion strain into the BSE strain: The origin of BSE? PLoS Pathog 3(3):
e31. doi:10.1371/journal.ppat.0030031


Introduction


snip...


Although BASE showed a significant barrier to primary
transmission to inbred mouse lines resulting in preclinical
infection, it remains of considerable concern whether the
causal agent is potentially pathogenic for humans. In this
regard, the neuropathological and molecular features of
BASE—in particular, the biochemical type and deposition
patterns of PrPSc—have striking similarities with those of a
distinct subgroup of patients with sporadic CJD [16]. This
finding requires a cautious interpretation. Nonetheless, the
possibility that the origin of CJD in some patients with a
sporadic disease phenotype may be related to BASE exposure
has to be considered and verified through transmission studies.


see full text ;


http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&blobtype=pdf&artid=1817656



USA MAD COW STRAIN MORE VIRULENT TO HUMANS THAN UK STRAIN

18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7
December 2006 are now available.


snip...



64. A member noted that at the recent Neuroprion meeting, a study was
presented showing that in transgenic mice BSE passaged in sheep may be more
virulent and infectious to a wider range of species than bovine derived BSE.

Other work presented suggested that BSE and bovine amyloidotic spongiform
encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the
prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A
MUTATION FOUND IN CASES OF SPORADIC CJD.


snip...



http://www.seac.gov.uk/minutes/95.pdf




3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse

Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve
University

Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain
discovered recently in Italy, and similar or different atypical BSE cases
were also reported in other countries. The infectivity and phenotypes of
these atypical BSE strains in humans are unknown. In collaboration with
Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have
inoculated transgenic mice expressing human prion protein with brain
homogenates from BASE or BSE infected cattle. Our data shows that about half
of the BASE-inoculated mice became infected with an average incubation time
of about 19 months; in contrast, none of the BSE-inoculated mice appear to
be infected after more than 2 years.

***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than
classical BSE in humans.***


6:30 Close of Day One


http://www.healthtech.com/2007/tse/day1.asp




SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM
1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...


http://www.cjdsurveillance.com/resources-casereport.html



There is a growing number of human CJD cases, and they were presented last
week in San Francisco by Luigi Gambatti(?) from his CJD surveillance
collection.

He estimates that it may be up to 14 or 15 persons which display selectively
SPRPSC and practically no detected RPRPSC proteins.


http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm


http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf



Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.

http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535


BRITISH MEDICAL JOURNAL

BMJ

http://www.bmj.com/cgi/eletters/319/7220/1312/b#EL2


BMJ

http://www.bmj.com/cgi/eletters/320/7226/8/b#EL1


JOURNAL OF NEUROLOGY

MARCH 26, 2003

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob

disease in the United States

Email Terry S. Singeltary:

[email protected]

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to

comment on the CDC's attempts to monitor the occurrence of emerging

forms of CJD. Asante, Collinge et al [1] have reported that BSE

transmission to the 129-methionine genotype can lead to an alternate

phenotype that is indistinguishable from type 2 PrPSc, the commonest

sporadic CJD. However, CJD and all human TSEs are not reportable

nationally. CJD and all human TSEs must be made reportable in every

state and internationally. I hope that the CDC does not continue to

expect us to still believe that the 85%+ of all CJD cases which are

sporadic are all spontaneous, without route/source. We have many TSEs in

the USA in both animal and man. CWD in deer/elk is spreading rapidly and

CWD does transmit to mink, ferret, cattle, and squirrel monkey by

intracerebral inoculation. With the known incubation periods in other

TSEs, oral transmission studies of CWD may take much longer. Every

victim/family of CJD/TSEs should be asked about route and source of this

agent. To prolong this will only spread the agent and needlessly expose

others. In light of the findings of Asante and Collinge et al, there

should be drastic measures to safeguard the medical and surgical arena

from sporadic CJDs and all human TSEs. I only ponder how many sporadic

CJDs in the USA are type 2 PrPSc?

http://www.neurology.org/cgi/eletters/60/2/176#535



Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
 
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