{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:54:40Z","timestamp":1768586080757,"version":"3.49.0"},"reference-count":23,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2003,5,1]],"date-time":"2003-05-01T00:00:00Z","timestamp":1051747200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2003,5]]},"abstract":"<jats:p> Infection with influenza A (H5N1) virus, which has not been associated with respiratory disease in humans previously, caused clinical signs of acute respiratory distress syndrome and multiple-organ dysfunction syndrome with high mortality in humans in Hong Kong in 1997. To study the pathogenesis of this disease, we infected four cynomolgus monkeys ( Macaca fascicularis) with 2.5 \u00d7 10<jats:sup>4<\/jats:sup> median tissue culture infectious dose (TCID<jats:sub>50<\/jats:sub>) of influenza virus A\/Hong Kong\/156\/97 (H5N1) and euthanatized them 4 or 7 days after infection. The main lesion was a necrotizing broncho-interstitial pneumonia (4\/4) similar to those found in primary influenza virus pneumonia in humans, with desquamation of respiratory epithelium (4\/4), intra-alveolar hemorrhage (4\/4), hyaline membrane formation (2\/4), and infiltration with neutrophils and macrophages (4\/4). Lesions in other organs consisted of a suppurative tonsillitis (2\/4) and necrosis in lymphoid organs (1\/4), kidney (1\/4), and liver (1\/4). By immunohistochemistry, influenza virus antigen was limited to pulmonary tissue (4\/4) and tonsils (2\/4). Based on these results, we suggest that the cynomolgus monkey is a suitable animal model for studying the pathogenesis of human H5N1 virus infection and that multiple-organ dysfunction syndrome in this disease may be caused by diffuse alveolar damage from virus replication in the lungs alone. <\/jats:p>","DOI":"10.1354\/vp.40-3-304","type":"journal-article","created":{"date-parts":[[2003,4,29]],"date-time":"2003-04-29T22:59:04Z","timestamp":1051657144000},"page":"304-310","source":"Crossref","is-referenced-by-count":108,"title":["Pathology of Human Influenza A (H5N1) Virus Infection in Cynomolgus Macaques (<i>Macaca fascicularis<\/i>)"],"prefix":"10.1177","volume":"40","author":[{"given":"T.","family":"Kuiken","sequence":"first","affiliation":[{"name":"Institute of Virology, National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. F.","family":"Rimmelzwaan","sequence":"additional","affiliation":[{"name":"Institute of Virology, National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Van Amerongen","sequence":"additional","affiliation":[{"name":"Institute of Virology, National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. D. M. E.","family":"Osterhaus","sequence":"additional","affiliation":[{"name":"Institute of Virology, National Influenza Center, Erasmus Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2003,5,1]]},"reference":[{"key":"bibr1-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510270072043"},{"key":"bibr2-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1941.43"},{"key":"bibr3-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)11212-0"},{"key":"bibr4-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012195160-3\/50004-2"},{"key":"bibr5-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1038\/39218"},{"key":"bibr6-vp.40-3-304","first-page":"2567","volume-title":"Fishman's Pulmonary Diseases and Disorders","author":"Deutschman CS","year":"1998","edition":"3"},{"key":"bibr7-vp.40-3-304","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S0272-5231(21)00757-7","volume":"11","author":"Dorinsky PM","year":"1990","journal-title":"Clin Chest Med"},{"key":"bibr8-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.3.1443-1450.2000"},{"key":"bibr9-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.4.3184-3189.1999"},{"key":"bibr10-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.7.5903-5911.1999"},{"key":"bibr11-vp.40-3-304","first-page":"1397","volume-title":"Fields Virology","author":"Murphy BR","year":"1996","edition":"3"},{"key":"bibr12-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-81-10-2503"},{"key":"bibr13-vp.40-3-304","first-page":"25","volume-title":"Advanced Laboratory Techniques for Influenza Diagnosis: Procedural Guide","author":"Palmer DF","year":"1975"},{"key":"bibr14-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.44.4.297"},{"key":"bibr15-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(84)80194-X"},{"key":"bibr16-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-0934(98)00071-8"},{"key":"bibr17-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.14.6687-6691.2001"},{"key":"bibr18-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012775390-4\/50257-8"},{"key":"bibr19-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5349.393"},{"key":"bibr20-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9071(200103)63:3<242::AID-JMV1007>3.0.CO;2-N"},{"key":"bibr21-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-3935-0_12"},{"key":"bibr22-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.3109\/00365548909039965"},{"key":"bibr23-vp.40-3-304","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)01182-9"}],"container-title":["Veterinary Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1354\/vp.40-3-304","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1354\/vp.40-3-304","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1354\/vp.40-3-304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T11:30:18Z","timestamp":1740915018000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1354\/vp.40-3-304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,5]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,5]]}},"alternative-id":["10.1354\/vp.40-3-304"],"URL":"https:\/\/doi.org\/10.1354\/vp.40-3-304","relation":{},"ISSN":["0300-9858","1544-2217"],"issn-type":[{"value":"0300-9858","type":"print"},{"value":"1544-2217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,5]]}}}