1887

Journal of General Virology header logo

Volume 94, Issue 6

Targeted knock-down of cellular prion protein expression in myelinating Schwann cells does not alter mouse prion pathogenesis Free

Abstract

In naturally acquired transmissible spongiform encephalopathies, the pathogenic agents or prions spread from the sites of initial peripheral uptake or replication to the brain where they cause progressive and fatal neurodegeneration. Routing via the peripheral nervous system is considered to be one of the main pathways to the central nervous system. Replication of prions in Schwann cells is viewed as a potentially important mechanism for efficient prion spread along nerves. Here we used a Cre-P mouse transgenetic approach to disrupt host-encoded prion protein (PrP) specifically in myelinating Schwann cells. Despite the use of infection routes targeting highly myelinated nerves, there was no alteration in mouse prion pathogenesis, suggesting that conversion-dependent, centripetal spread of prions does not crucially rely on PrP expressed by myelinating Schwann cells.

  • Received:
  • Accepted:
  • Published Online:
© 2013 SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.049619-0
2013-06-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/94/6/1435.html?itemId=/content/journal/jgv/10.1099/vir.0.049619-0&mimeType=html&fmt=ahah

References

  1. Aguzzi A. 2003; Prions and the immune system: a journey through gut, spleen, and nerves. Adv Immunol 81:123–171 [View Article][PubMed]
     [Google Scholar]
  2. Archer F., Bachelin C., Andreoletti O., Besnard N., Perrot G., Langevin C., Le Dur A., Vilette D., Baron-Van Evercooren A. other authors 2004; Cultured peripheral neuroglial cells are highly permissive to sheep prion infection. J Virol 78:482–490 [View Article][PubMed]
     [Google Scholar]
  3. Aucouturier P., Geissmann F., Damotte D., Saborio G. P., Meeker H. C., Kascsak R., Kascsak R., Carp R. I., Wisniewski T. 2001; Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie. J Clin Invest 108:703–708[PubMed] [CrossRef]
     [Google Scholar]
  4. Beekes M., McBride P. A., Baldauf E. 1998; Cerebral targeting indicates vagal spread of infection in hamsters fed with scrapie. J Gen Virol 79:601–607[PubMed]
     [Google Scholar]
  5. Beringue V., Lasmézas C. I., Adjou K. T., Demaimay R., Lamoury F., Deslys J. P., Seman M., Dormont D. 1999; Inhibiting scrapie neuroinvasion by polyene antibiotic treatment of SCID mice. J Gen Virol 80:1873–1877[PubMed]
     [Google Scholar]
  6. Béringue V., Vilotte J. L., Laude H. 2008a; Prion agent diversity and species barrier. Vet Res 39:47 [View Article][PubMed]
     [Google Scholar]
  7. Béringue V., Le Dur A., Tixador P., Reine F., Lepourry L., Perret-Liaudet A., Haïk S., Vilotte J. L., Fontés M., Laude H. 2008b; Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. PLoS ONE 3:e1419 [View Article][PubMed]
     [Google Scholar]
  8. Blättler T., Brandner S., Raeber A. J., Klein M. A., Voigtländer T., Weissmann C., Aguzzi A. 1997; PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain. Nature 389:69–73 [View Article][PubMed]
     [Google Scholar]
  9. Bradford B. M., Tuzi N. L., Feltri M. L., McCorquodale C., Cancellotti E., Manson J. C. 2009; Dramatic reduction of PrP C level and glycosylation in peripheral nerves following PrP knock-out from Schwann cells does not prevent transmissible spongiform encephalopathy neuroinvasion. J Neurosci 29:15445–15454 [View Article][PubMed]
     [Google Scholar]
  10. Bremer J., Baumann F., Tiberi C., Wessig C., Fischer H., Schwarz P., Steele A. D., Toyka K. V., Nave K. A. other authors 2010; Axonal prion protein is required for peripheral myelin maintenance. Nat Neurosci 13:310–318 [View Article][PubMed]
     [Google Scholar]
  11. Cancellotti E., Bradford B. M., Tuzi N. L., Hickey R. D., Brown D., Brown K. L., Barron R. M., Kisielewski D., Piccardo P., Manson J. C. 2010; Glycosylation of PrPC determines timing of neuroinvasion and targeting in the brain following transmissible spongiform encephalopathy infection by a peripheral route. J Virol 84:3464–3475 [View Article][PubMed]
     [Google Scholar]
  12. Collinge J. 2001; Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 24:519–550 [View Article][PubMed]
     [Google Scholar]
  13. Feltri M. L., Graus Porta D., Previtali S. C., Nodari A., Migliavacca B., Cassetti A., Littlewood-Evans A., Reichardt L. F., Messing A. other authors 2002; Conditional disruption of beta 1 integrin in Schwann cells impedes interactions with axons. J Cell Biol 156:199–210 [View Article][PubMed]
     [Google Scholar]
  14. Féraudet C., Morel N., Simon S., Volland H., Frobert Y., Créminon C., Vilette D., Lehmann S., Grassi J. 2005; Screening of 145 anti-PrP monoclonal antibodies for their capacity to inhibit PrPSc replication in infected cells. J Biol Chem 280:11247–11258 [View Article][PubMed]
     [Google Scholar]
  15. Follet J., Lemaire-Vieille C., Blanquet-Grossard F., Podevin-Dimster V., Lehmann S., Chauvin J. P., Decavel J. P., Varea R., Grassi J. other authors 2002; PrP expression and replication by Schwann cells: implications in prion spreading. J Virol 76:2434–2439 [View Article][PubMed]
     [Google Scholar]
  16. Ford M. J., Burton L. J., Morris R. J., Hall S. M. 2002; Selective expression of prion protein in peripheral tissues of the adult mouse. Neuroscience 113:177–192 [View Article][PubMed]
     [Google Scholar]
  17. Glatzel M., Aguzzi A. 2000; PrP(C) expression in the peripheral nervous system is a determinant of prion neuroinvasion. J Gen Virol 81:2813–2821[PubMed]
     [Google Scholar]
  18. Groschup M. H., Beekes M., McBride P. A., Hardt M., Hainfellner J. A., Budka H. 1999; Deposition of disease-associated prion protein involves the peripheral nervous system in experimental scrapie. Acta Neuropathol 98:453–457 [View Article][PubMed]
     [Google Scholar]
  19. Halata Z., Munger B. L. 1983; The sensory innervation of primate facial skin. II. Vermilion border and mucosa of lip. Brain Res 286:81–107[PubMed] [CrossRef]
     [Google Scholar]
  20. Hansen C., Li J. Y. 2012; Beyond α-synuclein transfer: pathology propagation in Parkinson’s disease. Trends Mol Med 18:248–255 [View Article][PubMed]
     [Google Scholar]
  21. Heikenwalder M., Julius C., Aguzzi A. 2007; Prions and peripheral nerves: a deadly rendezvous. J Neurosci Res 85:2714–2725 [View Article][PubMed]
     [Google Scholar]
  22. Kimberlin R. H., Walker C. A. 1988; Incubation periods in six models of intraperitoneally injected scrapie depend mainly on the dynamics of agent replication within the nervous system and not the lymphoreticular system. J Gen Virol 69:2953–2960 [View Article][PubMed]
     [Google Scholar]
  23. Kimberlin R. H., Hall S. M., Walker C. A. 1983; Pathogenesis of mouse scrapie. Evidence for direct neural spread of infection to the CNS after injection of sciatic nerve. J Neurol Sci 61:315–325 [View Article][PubMed]
     [Google Scholar]
  24. Klingeborn M., Race B., Meade-White K. D., Rosenke R., Striebel J. F., Chesebro B. 2011; Crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection. J Virol 85:1484–1494 [View Article][PubMed]
     [Google Scholar]
  25. Kratzel C., Krüger D., Beekes M. 2007a; Prion propagation in a nerve conduit model containing segments devoid of axons. J Gen Virol 88:3479–3485 [View Article][PubMed]
     [Google Scholar]
  26. Kratzel C., Mai J., Madela K., Beekes M., Krüger D. 2007b; Propagation of scrapie in peripheral nerves after footpad infection in normal and neurotoxin exposed hamsters. Vet Res 38:127–139 [View Article][PubMed]
     [Google Scholar]
  27. Künzi V., Glatzel M., Nakano M. Y., Greber U. F., Van Leuven F., Aguzzi A. 2002; Unhampered prion neuroinvasion despite impaired fast axonal transport in transgenic mice overexpressing four-repeat tau. J Neurosci 22:7471–7477[PubMed]
     [Google Scholar]
  28. Labetoulle M., Maillet S., Efstathiou S., Dezelee S., Frau E., Lafay F. 2003; HSV1 latency sites after inoculation in the lip: assessment of their localization and connections to the eye. Invest Ophthalmol Vis Sci 44:217–225 [View Article][PubMed]
     [Google Scholar]
  29. Langevin C., Andréoletti O., Le Dur A., Laude H., Béringue V. 2011; Marked influence of the route of infection on prion strain apparent phenotype in a scrapie transgenic mouse model. Neurobiol Dis 41:219–225 [View Article][PubMed]
     [Google Scholar]
  30. Lasmézas C. I., Cesbron J. Y., Deslys J. P., Demaimay R., Adjou K. T., Rioux R., Lemaire C., Locht C., Dormont D. 1996; Immune system-dependent and -independent replication of the scrapie agent. J Virol 70:1292–1295[PubMed]
     [Google Scholar]
  31. Mabbott N. A., Young J., McConnell I., Bruce M. E. 2003; Follicular dendritic cell dedifferentiation by treatment with an inhibitor of the lymphotoxin pathway dramatically reduces scrapie susceptibility. J Virol 77:6845–6854 [View Article][PubMed]
     [Google Scholar]
  32. Magalhães A. C., Baron G. S., Lee K. S., Steele-Mortimer O., Dorward D., Prado M. A., Caughey B. 2005; Uptake and neuritic transport of scrapie prion protein coincident with infection of neuronal cells. J Neurosci 25:5207–5216 [View Article][PubMed]
     [Google Scholar]
  33. Mallucci G. R., Ratté S., Asante E. A., Linehan J., Gowland I., Jefferys J. G., Collinge J. 2002; Post-natal knockout of prion protein alters hippocampal CA1 properties, but does not result in neurodegeneration. EMBO J 21:202–210 [View Article][PubMed]
     [Google Scholar]
  34. Mallucci G., Dickinson A., Linehan J., Klöhn P. C., Brandner S., Collinge J. 2003; Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 302:871–874 [View Article][PubMed]
     [Google Scholar]
  35. Mallucci G. R., White M. D., Farmer M., Dickinson A., Khatun H., Powell A. D., Brandner S., Jefferys J. G., Collinge J. 2007; Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected mice. Neuron 53:325–335 [View Article][PubMed]
     [Google Scholar]
  36. Maro G. S., Vermeren M., Voiculescu O., Melton L., Cohen J., Charnay P., Topilko P. 2004; Neural crest boundary cap cells constitute a source of neuronal and glial cells of the PNS. Nat Neurosci 7:930–938 [View Article][PubMed]
     [Google Scholar]
  37. McBride P. A., Schulz-Schaeffer W. J., Donaldson M., Bruce M., Diringer H., Kretzschmar H. A., Beekes M. 2001; Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves. J Virol 75:9320–9327 [View Article][PubMed]
     [Google Scholar]
  38. Michel B., Meyerett-Reid C., Johnson T., Ferguson A., Wyckoff C., Pulford B., Bender H., Avery A., Telling G. other authors 2012; Incunabular immunological events in prion trafficking. Sci Rep 2:440 [View Article][PubMed]
     [Google Scholar]
  39. Prinz M., Montrasio F., Klein M. A., Schwarz P., Priller J., Odermatt B., Pfeffer K., Aguzzi A. 2002; Lymph nodal prion replication and neuroinvasion in mice devoid of follicular dendritic cells. Proc Natl Acad Sci U S A 99:919–924 [View Article][PubMed]
     [Google Scholar]
  40. Prinz M., Montrasio F., Furukawa H., van der Haar M. E., Schwarz P., Rülicke T., Giger O. T., Häusler K. G., Perez D. other authors 2004; Intrinsic resistance of oligodendrocytes to prion infection. J Neurosci 24:5974–5981 [View Article][PubMed]
     [Google Scholar]
  41. Race R., Oldstone M., Chesebro B. 2000; Entry versus blockade of brain infection following oral or intraperitoneal scrapie administration: role of prion protein expression in peripheral nerves and spleen. J Virol 74:828–833 [View Article][PubMed]
     [Google Scholar]
  42. Topilko P., Schneider-Maunoury S., Levi G., Baron-Van Evercooren A., Chennoufi A. B., Seitanidou T., Babinet C., Charnay P. 1994; Krox-20 controls myelination in the peripheral nervous system. Nature 371:796–799 [View Article][PubMed]
     [Google Scholar]
  43. Voiculescu O., Charnay P., Schneider-Maunoury S. 2000; Expression pattern of a Krox-20/Cre knock-in allele in the developing hindbrain, bones, and peripheral nervous system. Genesis 26:123–126 [View Article][PubMed]
     [Google Scholar]
  44. Westergard L., Turnbaugh J. A., Harris D. A. 2011; A naturally occurring C-terminal fragment of the prion protein (PrP) delays disease and acts as a dominant-negative inhibitor of PrPSc formation. J Biol Chem 286:44234–44242 [View Article][PubMed]
     [Google Scholar]
  45. Yu W. M., Yu H., Chen Z. L., Strickland S. 2009; Disruption of laminin in the peripheral nervous system impedes nonmyelinating Schwann cell development and impairs nociceptive sensory function. Glia 57:850–859 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.049619-0
Loading
Targeted knock-down of cellular prion protein expression in myelinating Schwann cells does not alter mouse prion pathogenesis
J. Gen. Virol. 94, 1435 (2013); https://doi.org/10.1099/vir.0.049619-0
/content/journal/jgv/10.1099/vir.0.049619-0
/content/journal/jgv/10.1099/vir.0.049619-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error