Emergence of classical BSE strain properties during serial passages of H-BSE in wild-type mice.
BACKGROUND
Two distinct forms of atypical spongiform encephalopathies (H-BSE and L-BSE) have recently been identified in cattle. Transmission studies in several wild-type or transgenic mouse models showed that these forms were associated with two distinct major strains of infectious agents, which also differed from the unique strain that had been isolated from cases of classical BSE during the food-borne epizootic disease.


RESULTS
H-BSE was monitored during three serial passages in C57BL/6 mice. On second passage, most of the inoculated mice showed molecular features of the abnormal prion protein (PrP(d)) and brain lesions similar to those observed at first passage, but clearly distinct from those of classical BSE in this mouse model. These features were similarly maintained during a third passage. However, on second passage, some of the mice exhibited distinctly different molecular and lesion characteristics, reminiscent of classical BSE in C57Bl/6 mice. These similarities were confirmed on third passage from such mice, for which the same survival time was also observed as with classical BSE adapted to C57Bl/6 mice. Lymphotropism was rarely detected in mice with H-BSE features. In contrast, PrP(d) was detectable, on third passage, in the spleens of most mice exhibiting classical BSE features, the pattern being indistinguishable from that found in C57Bl/6 mice infected with classical BSE.


CONCLUSIONS
Our data demonstrate the emergence of a prion strain with features similar to classical BSE during serial passages of H-BSE in wild-type mice. Such findings might help to explain the origin of the classical BSE epizootic disease, which could have originated from a putatively sporadic form of BSE.
Agence Française de Sécurité Sanitaire des Aliments-Lyon, Lyon, France. thierry.baron@anses.fr
Thierry
T
Baron
Johann
J
Vulin
Anne-Gaëlle
AG
Biacabe
Latefa
L
Lakhdar
Jérémy
J
Verchere
Juan-Maria
JM
Torres
Anna
A
Bencsik
D000818:Animals; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D051379:Mice; D008810:Mice, Inbred C57BL; D011328:Prions / Q000032:analysis* / Q000737:chemistry; D012692:Serial Passage; D013154:Spleen / Q000737:chemistry
D011328:Prions
Emerg Infect Dis. 2006 Jul;12(7):1125-8
16836832
PLoS Pathog. 2008 Aug 29;4(8):e1000137
18769714
J Comp Pathol. 1968 Jul;78(3):301-11
4970192
J Gen Virol. 1996 Jul;77 ( Pt 7):1601-9
8758005
Vet Microbiol. 2006 Oct 31;117(2-4):103-16
16916588
Emerg Infect Dis. 2008 Feb;14(2):298-300
18258124
J Gen Virol. 1992 Aug;73 ( Pt 8):1891-7
1645134
J Gen Virol. 1987 Jan;68 ( Pt 1):79-89
3100717
Vet Pathol. 2011 Sep;48(5):942-7
20921323
Lancet. 2006 Jan 28;367(9507):297-8; author reply 298-9
16443028
J Histochem Cytochem. 2006 Aug;54(8):849-53
16549507
PLoS Pathog. 2006 Oct;2(10):e112
17054396
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3065-70
14970340
Vet Rec. 1988 Dec 17;123(25):638-44
3218047
PLoS One. 2010 May 14;5(5):e10638
20498835
Histochem Cell Biol. 2007 May;127(5):531-9
17361441
PLoS Pathog. 2007 Mar;3(3):e31
17352534
EMBO Rep. 2004 Jan;5(1):110-5
14710195
J Vet Diagn Invest. 2007 Mar;19(2):142-54
17402608
Vet Rec. 2005 Apr 16;156(16):523-4
15833975
J Comp Pathol. 2006 Jan;134(1):17-29
16324707
Emerg Infect Dis. 2007 Dec;13(12):1887-94
18258040
Vaccine. 2007 Jul 26;25(30):5625-30
17126958
J Gen Virol. 1992 Feb;73 ( Pt 2):329-34
1531675
J Neurosci. 2007 Jun 27;27(26):6965-71
17596445
J Comp Pathol. 2005 Feb-Apr;132(2-3):117-31
15737338
J Gen Virol. 2010 Feb;91(Pt 2):570-4
19828761
Nature. 1997 Oct 2;389(6650):498-501
9333239
Nature. 1997 Apr 10;386(6625):564
9121579
PLoS One. 2010 Apr 26;5(4):e10310
20436680
J Virol Methods. 2005 Mar;124(1-2):197-202
15664069
Jpn J Infect Dis. 2007 Sep;60(5):305-8
17881874
Prion. 2007 Jan-Mar;1(1):61-8
19164888
J Clin Microbiol. 2007 Jun;45(6):1821-9
17442800
J Infect Dis. 1998 Sep;178(3):693-9
9728537
Philos Trans R Soc Lond B Biol Sci. 1994 Mar 29;343(1306):405-11
7913758
Nature. 1996 Oct 24;383(6602):685-90
8878476
PLoS Pathog. 2008 May 23;4(5):e1000075
18497860
Neuropathol Appl Neurobiol. 2003 Jun;29(3):262-72
12787323
J Virol. 2001 Jan;75(1):107-14
11119579
J Histochem Cytochem. 2006 Oct;54(10):1087-94
16735593