Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Aug 29;97(18):10248-53.
doi: 10.1073/pnas.97.18.10248.

Species-barrier-independent prion replication in apparently resistant species

A F Hill  1 , S Joiner, J Linehan, M Desbruslais, P L Lantos, J Collinge
Affiliations

Species-barrier-independent prion replication in apparently resistant species

A F Hill et al. Proc Natl Acad Sci U S A. .

Abstract

Transmission of prions between mammalian species is thought to be limited by a "species barrier," which depends on differences in the primary structure of prion proteins in the infecting inoculum and the host. Here we demonstrate that a strain of hamster prions thought to be nonpathogenic for conventional mice leads to prion replication to high levels in such mice but without causing clinical disease. Prions pathogenic in both mice and hamsters are produced. These results demonstrate the existence of subclinical forms of prion infection with important public health implications, both with respect to iatrogenic transmission from apparently healthy humans and dietary exposure to cattle and other species exposed to bovine spongiform encephalopathy prions. Current definitions of the species barrier, which have been based on clinical end-points, need to be fundamentally reassessed.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Western blot analysis of brain homogenates treated with proteinase K using anti-PrP antibodies R073, which detects both mouse and hamster PrP (lanes 1–3) and 3F4, which detects hamster PrP only (lanes 4–6) (40). Lanes 1 and 4: Sc237-inoculated hamster; lanes 2 and 5: Sc237-inoculated CD-1 mouse positive for murine PrPSc; lanes 3 and 6: Sc237-inoculated mouse negative for PrPSc. Numbers adjacent to horizontal lines indicate positions of molecular mass markers (kDa). Ten microliters of a 10% brain homogenate was loaded in each lane.
Figure 2
Figure 2
Neuropathological examination of Sc237-inoculated (a) and (b) and PBS-inoculated (c) and (d) CD-1 mice (41). (a and c) Hematoxylin- and eosin-stained sections showing spongiform neurodegeneration in a. (b and d) PrP immunohistochemistry showing abnormal PrP immunoreactivity including PrP-positive plaques in b. (c and d) Normal appearances. Magnifications: ×150.
Figure 3
Figure 3
Western blot analysis of proteinase K-treated brain homogenates using anti-PrP antibody R073 to determine PrPSc types (40). Lane 1: Sc237-inoculated Syrian hamster; lane 2: Sc237-inoculated CD-1 mouse; lanes 3–5: passage of Sc237-inoculated CD-1 mouse into Syrian hamster (lane 3), CD-1 mouse (lane 4), and Tg20 mouse (lane 5). Numbers adjacent to horizontal lines indicate positions of molecular mass markers (kDa).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Prions: Beyond a Single Protein.
    Das AS, Zou WQ. Das AS, et al. Clin Microbiol Rev. 2016 Jul;29(3):633-58. doi: 10.1128/CMR.00046-15. Clin Microbiol Rev. 2016. PMID: 27226089 Free PMC article. Review.
  • Porcine prion protein amyloid.
    Hammarström P, Nyström S. Hammarström P, et al. Prion. 2015;9(4):266-77. doi: 10.1080/19336896.2015.1065373. Prion. 2015. PMID: 26218890 Free PMC article.
  • Rabbits are not resistant to prion infection.
    Chianini F, Fernández-Borges N, Vidal E, Gibbard L, Pintado B, de Castro J, Priola SA, Hamilton S, Eaton SL, Finlayson J, Pang Y, Steele P, Reid HW, Dagleish MP, Castilla J. Chianini F, et al. Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5080-5. doi: 10.1073/pnas.1120076109. Epub 2012 Mar 13. Proc Natl Acad Sci U S A. 2012. PMID: 22416127 Free PMC article.
  • Formation of native prions from minimal components in vitro.
    Deleault NR, Harris BT, Rees JR, Supattapone S. Deleault NR, et al. Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9741-6. doi: 10.1073/pnas.0702662104. Epub 2007 May 29. Proc Natl Acad Sci U S A. 2007. PMID: 17535913 Free PMC article.
  • Subclinical infection occurs frequently following low dose exposure to prions by blood transfusion.
    Salamat MKF, Stewart P, Brown H, Tan KBC, Smith A, de Wolf C, Alejo Blanco AR, Turner M, Manson JC, McCutcheon S, Houston EF. Salamat MKF, et al. Sci Rep. 2022 Jun 28;12(1):10923. doi: 10.1038/s41598-022-15105-w. Sci Rep. 2022. PMID: 35764688 Free PMC article.
See all "Cited by" articles

References

    1. Griffith J S. Nature (London) 1967;215:1043–1044. - PubMed
    1. Prusiner S B. Science. 1982;216:136–144. - PubMed
    1. Pattison I H. In: Slow, Latent and Temperate Virus Infections, NINDB Monograph 2. Gajdusek C J, Gibbs C J, Alpers M P, editors. Washington DC: U.S. Government Printing; 1965. pp. 249–257.
    1. Collinge J, Sidle K C L, Meads J, Ironside J, Hill A F. Nature (London) 1996;383:685–690. - PubMed
    1. Hill A F, Desbruslais M, Joiner S, Sidle K C L, Gowland I, Collinge J. Nature (London) 1997;389:448–450. - PubMed

Publication types

LinkOut - more resources