{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:04:48Z","timestamp":1791291888857,"version":"4.1.0"},"reference-count":16,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,3,30]]},"abstract":"<jats:p>Experimental lemurs either were infected orally with the agent of bovine spongiform encephalopathy (BSE) or were maintained as uninfected control animals. Immunohistochemical examination for proteinase-resistant protein (prion protein or PrP) was performed on tissues from two infected but still asymptomatic lemurs, killed 5 months after infection, and from three uninfected control lemurs. Control tissues showed no staining, whereas PrP was detected in the infected animals in tonsil, gastrointestinal tract and associated lymphatic tissues, and spleen. In addition, PrP was detected in ventral and dorsal roots of the cervical spinal cord, and within the spinal cord PrP could be traced in nerve tracts as far as the cerebral cortex. Similar patterns of PrP immunoreactivity were seen in two symptomatic and 18 apparently healthy lemurs in three different French primate centers, all of which had been fed diets supplemented with a beef protein product manufactured by a British company that has since ceased to include beef in its veterinary nutritional products. This study of BSE-infected lemurs early in their incubation period extends previous pathogenesis studies of the distribution of infectivity and PrP in natural and experimental scrapie. The similarity of neuropathology and PrP immunostaining patterns in experimentally infected animals to those observed in both symptomatic and asymptomatic animals in primate centers suggests that BSE contamination of zoo animals may have been more widespread than is generally appreciated.<\/jats:p>","DOI":"10.1073\/pnas.96.7.4046","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:42:40Z","timestamp":1027680160000},"page":"4046-4051","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":140,"title":["Natural and experimental oral infection of nonhuman primates by bovine spongiform encephalopathy agents"],"prefix":"10.1073","volume":"96","author":[{"given":"N\u00f6elle","family":"Bons","sequence":"first","affiliation":[{"name":"Ecole Pratique des Hautes Etudes, Laboratoire de Neuromorphologie Fonctionnelle, Universit\u00e9 Montpellier II, 34095-Montpellier cedex 5, France; Centre National d\u2019Etudes Veterinaires et Alimentaires, Pathologie Bovine, 31 Av. Tony Garnier, 69342-Lyon cedex 07, France; 68 Bd Saint-Michel, 75006-Paris, France; Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198-Gif-sur-Yvette, France; and Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Mestre-Frances","sequence":"additional","affiliation":[{"name":"Ecole Pratique des Hautes Etudes, Laboratoire de Neuromorphologie Fonctionnelle, Universit\u00e9 Montpellier II, 34095-Montpellier cedex 5, France; Centre National d\u2019Etudes Veterinaires et Alimentaires, Pathologie Bovine, 31 Av. Tony Garnier, 69342-Lyon cedex 07, France; 68 Bd Saint-Michel, 75006-Paris, France; Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198-Gif-sur-Yvette, France; and Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Belli","sequence":"additional","affiliation":[{"name":"Ecole Pratique des Hautes Etudes, Laboratoire de Neuromorphologie Fonctionnelle, Universit\u00e9 Montpellier II, 34095-Montpellier cedex 5, France; Centre National d\u2019Etudes Veterinaires et Alimentaires, Pathologie Bovine, 31 Av. Tony Garnier, 69342-Lyon cedex 07, France; 68 Bd Saint-Michel, 75006-Paris, France; Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198-Gif-sur-Yvette, France; and Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Cathala","sequence":"additional","affiliation":[{"name":"Ecole Pratique des Hautes Etudes, Laboratoire de Neuromorphologie Fonctionnelle, Universit\u00e9 Montpellier II, 34095-Montpellier cedex 5, France; Centre National d\u2019Etudes Veterinaires et Alimentaires, Pathologie Bovine, 31 Av. Tony Garnier, 69342-Lyon cedex 07, France; 68 Bd Saint-Michel, 75006-Paris, France; Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198-Gif-sur-Yvette, France; and Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Carleton","family":"Gajdusek","sequence":"additional","affiliation":[{"name":"Ecole Pratique des Hautes Etudes, Laboratoire de Neuromorphologie Fonctionnelle, Universit\u00e9 Montpellier II, 34095-Montpellier cedex 5, France; Centre National d\u2019Etudes Veterinaires et Alimentaires, Pathologie Bovine, 31 Av. Tony Garnier, 69342-Lyon cedex 07, France; 68 Bd Saint-Michel, 75006-Paris, France; Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198-Gif-sur-Yvette, France; and Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Brown","sequence":"additional","affiliation":[{"name":"Ecole Pratique des Hautes Etudes, Laboratoire de Neuromorphologie Fonctionnelle, Universit\u00e9 Montpellier II, 34095-Montpellier cedex 5, France; Centre National d\u2019Etudes Veterinaires et Alimentaires, Pathologie Bovine, 31 Av. Tony Garnier, 69342-Lyon cedex 07, France; 68 Bd Saint-Michel, 75006-Paris, France; Institut Alfred Fessard, Centre National de la Recherche Scientifique, 91198-Gif-sur-Yvette, France; and Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,3,30]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)24027-9"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0764-4469(97)82470-5"},{"key":"e_1_3_3_3_2","first-page":"265","volume-title":"Methods in Molecular Medicine: Prion Diseases","author":"Tagliavini F","year":"1996","unstructured":"F Tagliavini, F Prelli, G Giaccone, G Forloni, M Salmona, P Piccardo, B Ghetti, B Frangione, O Bugiani Methods in Molecular Medicine: Prion Diseases, eds H Baker, M Ridley (Humana, Totowa, NJ), pp. 265\u2013283 (1996)."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308912"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(97)00458-9"},{"key":"e_1_3_3_6_2","first-page":"77","volume":"318","author":"Bons N","year":"1995","unstructured":"N Bons, V Jallageas, S Silhol, N Mestre-Franc\u00e9s, A Petter, A Delacourte C R Acad Sci 318, 77\u201383 (1995).","journal-title":"C R Acad Sci"},{"key":"e_1_3_3_7_2","first-page":"85","volume":"318","author":"Delacourte A","year":"1995","unstructured":"A Delacourte, P E Sauti\u00e8re, A Wattez, C Mourton-Gilles, A Petter, N Bons C R Acad Sci 318, 85\u201389 (1995).","journal-title":"C R Acad Sci"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/117.1.15"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/129.5.559"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/146.5.657"},{"key":"e_1_3_3_11_2","first-page":"37","volume-title":"Novel Infectious Agents and the Central Nervous System","author":"Kimberlin R H","year":"1988","unstructured":"R H Kimberlin, C A Walker Novel Infectious Agents and the Central Nervous System, eds G Bock, J Marsh (Wiley, Chichester, U.K.), pp. 37\u201362 (1988)."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1702(89)90040-3"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-77-8-1925"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-79-3-601"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/37789"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/vr.142.5.103"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.96.7.4046","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:49:06Z","timestamp":1649872146000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.96.7.4046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3,30]]},"references-count":16,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1999,3,30]]}},"alternative-id":["10.1073\/pnas.96.7.4046"],"URL":"https:\/\/doi.org\/10.1073\/pnas.96.7.4046","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,3,30]]},"assertion":[{"value":"1998-12-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-03-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}