Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.
Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrPC) and the infecting pathological PrP assemblies (PrPSc) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrPCand in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrPScsignatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD.


OBJECTIVE
Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population.
VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
Emilie
E
Jaumain
Neurobiology Laboratory, Biochemistry and Molecular Biology Department, Hôpitaux de Lyon, Lyon, France.|University of Lyon 1, CNRS UMR5292, INSERM U1028, BioRan, Lyon, France.
Isabelle
I
Quadrio
VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
Laetitia
L
Herzog
VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
Fabienne
F
Reine
VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
Human
H
Rezaei
IHAP, INRA, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
Olivier
O
Andréoletti
VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
Hubert
H
Laude
Neurobiology Laboratory, Biochemistry and Molecular Biology Department, Hôpitaux de Lyon, Lyon, France.|University of Lyon 1, CNRS UMR5292, INSERM U1028, BioRan, Lyon, France.
Armand
A
Perret-Liaudet
INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle Épinière, ICM, Paris, France.|Centre National de Référence des Agents Transmissibles Non Conventionnels, Paris, France.
Stéphane
S
Haïk
VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France vincent.beringue@inra.fr.
Vincent
V
Béringue
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000209:etiology / Q000235:genetics* / Q000635:transmission; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000209:etiology / Q000235:genetics* / Q000635:transmission; D014644:Genetic Variation; D058507:Host Specificity; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000235:genetics / Q000472:pathogenicity; D018620:PrPSc Proteins / Q000235:genetics / Q000472:pathogenicity
D018621:PrPC Proteins; D018620:PrPSc Proteins
PLoS Pathog. 2006 Feb;2(2):e12
16518470
BMC Res Notes. 2015 Jul 24;8:312
26205536
PLoS One. 2013 Jul 03;8(7):e66352
23843953
PLoS Pathog. 2012;8(3):e1002582
22479179
J Gen Virol. 1978 Jun;39(3):487-96
96212
Brain Pathol. 2016 Jan;26(1):95-101
25851836
J Virol. 1987 Dec;61(12):3688-93
2446004
J Gen Virol. 1989 Aug;70 ( Pt 8):2017-25
2504883
PLoS One. 2008 Jan 09;3(1):e1419
18183299
Am J Pathol. 2006 Mar;168(3):927-35
16507908
Emerg Infect Dis. 2008 Dec;14(12):1898-901
19046515
Vet Res. 2008 Jul-Aug;39(4):47
18519020
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363-83
9811807
Am J Pathol. 2004 Jan;164(1):143-53
14695328
Science. 2010 Feb 12;327(5967):869-72
20044542
J Virol. 2014 Aug;88(15):8678-86
24850746
J Gen Virol. 2012 Jul;93(Pt 7):1624-9
22495232
Acta Neuropathol Commun. 2016 Feb 05;4:10
26847207
Arch Virol. 2003 Apr;148(4):677-91
12664293
J Biol Chem. 2005 Mar 25;280(12):11247-58
15618225
J Neurosci. 2007 Jun 27;27(26):6965-71
17596445
Science. 2007 Nov 9;318(5852):930-6
17991853
N Engl J Med. 2003 Nov 6;349(19):1812-20
14602879
Emerg Infect Dis. 2008 Feb;14(2):298-300
18258124
J Clin Microbiol. 2016 Mar;54(3):676-86
26739160
EMBO J. 2002 Dec 2;21(23):6358-66
12456643
J Gen Virol. 2013 Dec;94(Pt 12):2819-27
24045112
Brain Pathol. 2012 Sep;22(5):662-9
22288561
Science. 2012 Jan 27;335(6067):472-5
22282814
MBio. 2013 Dec 31;5(1):e00829-13
24381300
Ann Neurol. 1999 Aug;46(2):224-33
10443888
EBioMedicine. 2016 Oct;12 :150-155
27612591
Nat Commun. 2014 Dec 16;5:5821
25510416
PLoS One. 2008 Aug 20;3(8):e3017
18714385
PLoS Pathog. 2014 Jun 12;10(6):e1004202
24945656
J Virol. 2008 Apr;82(7):3697-701
18234793
PLoS Pathog. 2008 Mar 14;4(3):e1000029
18389084
Ann Neurol. 1994 May;35(5):513-29
8179297
Br Med Bull. 2003;66:99-108
14522852
Protein Sci. 2001 Apr;10(4):854-63
11274476
Jpn J Infect Dis. 2011;64(1):81-4
21266763
Nat Rev Neurol. 2016 Jun;12(6):325-33
27174240
Br Med Bull. 2003;66:255-65
14522863
Brain. 2003 Jun;126(Pt 6):1333-46
12764055
Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):12005-10
20547859
Neurology. 1999 Dec 10;53(9):2173-6
10599800