Journal of General Virology, Vol 79, 601-607, Copyright © 1998 by Society for General Microbiology

ARTICLES

Cerebral targeting indicates vagal spread of infection in hamsters fed with scrapie

M Beekes, PA McBride and E Baldauf
Robert Koch-Institut, Bundesinstitut fur Infektionskrankheiten und nicht ubertragbare Krankheiten, Berlin, Germany. BeekesM@rki.de

The pathogenesis of scrapie and other transmissible spongiform encephalopathies (TSEs) following oral uptake of agent is still poorly understood and can best be studied in mice and hamsters. The experiments described here further extend the understanding of the pathways along which infection spreads from the periphery to the brain after an oral challenge with scrapie. Using TSE-specific amyloid protein (TSE-AP, also called PrP) as a marker for infectivity, immunohistochemical evidence suggested that the first target area in the brain of hamsters orally infected with scrapie is the dorsal motor nucleus of the vagus nerve (DMNV), rapidly followed by the commissural solitary tract nucleus (SN). The cervical spinal cord was affected only after TSE-AP had been deposited in the DMNV, SN and other medullary target areas. For the first time, these results demonstrate conclusively that, in our animal model, initial infection of the brain after oral ingestion of scrapie agent occurs via the vagus nerve, rather than by spread along the spinal cord.

This article has been cited by other articles:

				J D Bailey, J G Berardinelli, T E Rocke, and R A Bessen Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases J. Endocrinol., May 1, 2008; 197(2): 251 - 263. [Abstract] [Full Text] [PDF]

				C. von Poser-Klein, E. Flechsig, T. Hoffmann, P. Schwarz, H. Harms, R. Bujdoso, A. Aguzzi, and M. A. Klein Alteration of B-Cell Subsets Enhances Neuroinvasion in Mouse Scrapie Infection J. Virol., April 1, 2008; 82(7): 3791 - 3795. [Abstract] [Full Text] [PDF]

				C. Kratzel, D. Kruger, and M. Beekes Prion propagation in a nerve conduit model containing segments devoid of axons J. Gen. Virol., December 1, 2007; 88(12): 3479 - 3485. [Abstract] [Full Text] [PDF]

				M. E. Arnold, J. B. M. Ryan, T. Konold, M. M. Simmons, Y. I. Spencer, A. Wear, M. Chaplin, M. Stack, S. Czub, R. Mueller, et al. Estimating the temporal relationship between PrPSc detection and incubation period in experimental bovine spongiform encephalopathy of cattle J. Gen. Virol., November 1, 2007; 88(11): 3198 - 3208. [Abstract] [Full Text] [PDF]

				K. Masujin, D. Matthews, G. A. H. Wells, S. Mohri, and T. Yokoyama Prions in the peripheral nerves of bovine spongiform encephalopathy-affected cattle J. Gen. Virol., June 1, 2007; 88(6): 1850 - 1858. [Abstract] [Full Text] [PDF]

				A. E. Kincaid and J. C. Bartz The Nasal Cavity Is a Route for Prion Infection in Hamsters J. Virol., May 1, 2007; 81(9): 4482 - 4491. [Abstract] [Full Text] [PDF]

				G. Lalatta-Costerbosa, M. Mazzoni, P. Clavenzani, G. Di Guardo, G. Mazzuoli, G. Marruchella, L. De Grossi, U. Agrimi, and R. Chiocchetti Nitric Oxide Synthase Immunoreactivity and NADPH-d Histochemistry in the Enteric Nervous System of Sarda Breed Sheep With Different PrP Genotypes in Whole-mount and Cryostat Preparations J. Histochem. Cytochem., April 1, 2007; 55(4): 387 - 401. [Abstract] [Full Text] [PDF]

				S. Paquet, C. Langevin, J. Chapuis, G. S. Jackson, H. Laude, and D. Vilette Efficient dissemination of prions through preferential transmission to nearby cells J. Gen. Virol., February 1, 2007; 88(2): 706 - 713. [Abstract] [Full Text] [PDF]

				C. Cordier, A. Bencsik, S. Philippe, D. Betemps, F. Ronzon, D. Calavas, C. Crozet, and T. Baron Transmission and characterization of bovine spongiform encephalopathy sources in two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59) J. Gen. Virol., December 1, 2006; 87(12): 3763 - 3771. [Abstract] [Full Text] [PDF]

				K. A. Fox, J. E. Jewell, E. S. Williams, and M. W. Miller Patterns of PrPCWD accumulation during the course of chronic wasting disease infection in orally inoculated mule deer (Odocoileus hemionus). J. Gen. Virol., November 1, 2006; 87(Pt 11): 3451 - 3461. [Abstract] [Full Text] [PDF]

				C. DeJoia, B. Moreaux, K. O'Connell, and R. A. Bessen Prion Infection of Oral and Nasal Mucosa J. Virol., May 1, 2006; 80(9): 4546 - 4556. [Abstract] [Full Text] [PDF]

				E. S. Williams Chronic Wasting Disease Vet. Pathol., September 1, 2005; 42(5): 530 - 549. [Abstract] [Full Text] [PDF]

				J Collinge Molecular neurology of prion disease J. Neurol. Neurosurg. Psychiatry, July 1, 2005; 76(7): 906 - 919. [Abstract] [Full Text] [PDF]

				C Ishida, S Okino, T Kitamoto, and M Yamada Involvement of the peripheral nervous system in human prion diseases including dural graft associated Creutzfeldt-Jakob disease J. Neurol. Neurosurg. Psychiatry, March 1, 2005; 76(3): 325 - 329. [Abstract] [Full Text] [PDF]

				Z. Marcos, K. Pffeifer, M. E. Bodegas, M. P. Sesma, and L. Guembe Cellular Prion Protein Is Expressed in a Subset of Neuroendocrine Cells of the Rat Gastrointestinal Tract J. Histochem. Cytochem., October 1, 2004; 52(10): 1357 - 1365. [Abstract] [Full Text] [PDF]

				F. Archer, C. Bachelin, O. Andreoletti, N. Besnard, G. Perrot, C. Langevin, A. Le Dur, D. Vilette, A. Baron-Van Evercooren, J.-L. Vilotte, et al. Cultured Peripheral Neuroglial Cells Are Highly Permissive to Sheep Prion Infection J. Virol., January 1, 2004; 78(1): 482 - 490. [Abstract] [Full Text] [PDF]

				A. M. Thackray, M. A. Klein, and R. Bujdoso Subclinical Prion Disease Induced by Oral Inoculation J. Virol., July 15, 2003; 77(14): 7991 - 7998. [Abstract] [Full Text] [PDF]

				A. Aguzzi, F. L Heppner, M. Heikenwalder, M. Prinz, K. Mertz, H. Seeger, and M. Glatzel Immune system and peripheral nerves in propagation of prions to CNS Br. Med. Bull., June 1, 2003; 66(1): 141 - 159. [Abstract] [Full Text] [PDF]

				R. Heggebo, L. Gonzalez, C. McL. Press, G. Gunnes, A. Espenes, and M. Jeffrey Disease-associated PrP in the enteric nervous system of scrapie-affected Suffolk sheep J. Gen. Virol., May 1, 2003; 84(5): 1327 - 1338. [Abstract] [Full Text] [PDF]

				J. C. Bartz, A. E. Kincaid, and R. A. Bessen Rapid Prion Neuroinvasion following Tongue Infection J. Virol., December 6, 2002; 77(1): 583 - 591. [Abstract] [Full Text] [PDF]

				T. R. Spraker, R. R. Zink, B. A. Cummings, C. J. Sigurdson, M. W. Miller, and K. I. O'Rourke Distribution of Protease-resistant Prion Protein and Spongiform Encephalopathy in Free-ranging Mule Deer (Odocoileus hemionus) with Chronic Wasting Disease Vet. Pathol., September 1, 2002; 39(5): 546 - 556. [Abstract] [Full Text] [PDF]

				J. C. Bartz, A. E. Kincaid, and R. A. Bessen Retrograde Transport of Transmissible Mink Encephalopathy within Descending Motor Tracts J. Virol., May 8, 2002; 76(11): 5759 - 5768. [Abstract] [Full Text] [PDF]

				J. Kneipp, M. Beekes, P. Lasch, and D. Naumann Molecular Changes of Preclinical Scrapie Can Be Detected by Infrared Spectroscopy J. Neurosci., April 15, 2002; 22(8): 2989 - 2997. [Abstract] [Full Text] [PDF]

				M. B. A. Oldstone, R. Race, D. Thomas, H. Lewicki, D. Homann, S. Smelt, A. Holz, P. Koni, D. Lo, B. Chesebro, et al. Lymphotoxin-{alpha}- and Lymphotoxin-{beta}-Deficient Mice Differ in Susceptibility to Scrapie: Evidence against Dendritic Cell Involvement in Neuroinvasion J. Virol., March 27, 2002; 76(9): 4357 - 4363. [Abstract] [Full Text] [PDF]

				J. Follet, C. Lemaire-Vieille, F. Blanquet-Grossard, V. Podevin-Dimster, S. Lehmann, J.-P. Chauvin, J.-P. Decavel, R. Varea, J. Grassi, M. Fontes, et al. PrP Expression and Replication by Schwann Cells: Implications in Prion Spreading J. Virol., March 1, 2002; 76(5): 2434 - 2439. [Abstract] [Full Text] [PDF]

				P. A. McBride, W. J. Schulz-Schaeffer, M. Donaldson, M. Bruce, H. Diringer, H. A. Kretzschmar, and M. Beekes Early Spread of Scrapie from the Gastrointestinal Tract to the Central Nervous System Involves Autonomic Fibers of the Splanchnic and Vagus Nerves J. Virol., October 1, 2001; 75(19): 9320 - 9327. [Abstract] [Full Text] [PDF]

				N. A. Mabbott and M. E. Bruce The immunobiology of TSE diseases J. Gen. Virol., October 1, 2001; 82(10): 2307 - 2318. [Full Text] [PDF]

				C. J. Sigurdson, T. R. Spraker, M. W. Miller, B. Oesch, and E. A. Hoover PrPCWD in the myenteric plexus, vagosympathetic trunk and endocrine glands of deer with chronic wasting disease J. Gen. Virol., October 1, 2001; 82(10): 2327 - 2334. [Abstract] [Full Text] [PDF]

				M. Glatzel and A. Aguzzi PrPC expression in the peripheral nervous system is a determinant of prion neuroinvasion J. Gen. Virol., November 1, 2000; 81(11): 2813 - 2821. [Abstract] [Full Text]

				F. Montrasio, R. Frigg, M. Glatzel, M. A. Klein, F. Mackay, A. Aguzzi, and C. Weissmann Impaired Prion Replication in Spleens of Mice Lacking Functional Follicular Dendritic Cells Science, May 19, 2000; 288(5469): 1257 - 1259. [Abstract] [Full Text]

				N. A. Mabbott, A. Williams, C. F. Farquhar, M. Pasparakis, G. Kollias, and M. E. Bruce Tumor Necrosis Factor Alpha-Deficient, but Not Interleukin-6-Deficient, Mice Resist Peripheral Infection with Scrapie J. Virol., April 1, 2000; 74(7): 3338 - 3344. [Abstract] [Full Text]

				H. Rudyk, S. Vasiljevic, R. M. Hennion, C. R. Birkett, J. Hope, and I. H. Gilbert Screening Congo Red and its analogues for their ability to prevent the formation of PrP-res in scrapie-infected cells J. Gen. Virol., April 1, 2000; 81(4): 1155 - 1164. [Abstract] [Full Text]

				R. Race, M. Oldstone, and B. Chesebro Entry versus Blockade of Brain Infection following Oral or Intraperitoneal Scrapie Administration: Role of Prion Protein Expression in Peripheral Nerves and Spleen J. Virol., January 1, 2000; 74(2): 828 - 833. [Abstract] [Full Text]

				T. Maignien, C. I. Lasmé zas, V. Beringue, D. Dormont, and J.-P. Deslys Pathogenesis of the oral route of infection of mice with scrapie and bovine spongiform encephalopathy agents J. Gen. Virol., November 1, 1999; 80(11): 3035 - 3042. [Abstract] [Full Text]

				K Doh-ura, S Mohri, H Tashiro, T Kawashima, H Kikuchi, and T Iwaki Brain injury does not modify transmissible spongiform encephalopathy caused by intraperitoneal inoculation with Fukuoka-1 strain J. Gen. Virol., June 1, 1999; 80(6): 1551 - 1556. [Abstract]

				N. Bons, N. Mestre-Frances, P. Belli, F. Cathala, D. C. Gajdusek, and P. Brown Natural and experimental oral infection of nonhuman primates by bovine spongiform encephalopathy agents PNAS, March 30, 1999; 96(7): 4046 - 4051. [Abstract] [Full Text] [PDF]