{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:03:34Z","timestamp":1794006214923,"version":"4.8.0"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Brazilian Council of Scientific and Technological Development Agency","doi-asserted-by":"publisher","award":["457664\/2013-4"],"award-info":[{"award-number":["457664\/2013-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Brazilian Council of Scientific and Technological Development Agency","doi-asserted-by":"publisher","award":["303999\/2016-0"],"award-info":[{"award-number":["303999\/2016-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Yellow fever (YF), a non-contagious infectious disease, is endemic or enzootic to the tropical regions of the Americas and Africa. Periodic outbreaks or epidemics have a significant impact on public health. Programmed cell death, or apoptosis, is generally characterised by distinct morphological changes and energy-dependent biochemical pathways. In this study, we performed immunohistochemistry analysis to identify and quantify proteases and protein targets involved in the cascade that triggers apoptosis in YF virus (YFV)-infected human hepatocytes. Liver tissue samples were collected from 26 individuals, among whom 21 were diagnosed as YF-positive, and five were flavivirus-negative and died due to other causes. The histopathological alterations in YFV-positive cases were characterised by the presence of apoptotic bodies, steatosis, cellular swelling, and extensive necrosis and haemorrhage in the hepatic lobules. Additionally, we observed an abundance of inflammatory infiltrates in the portal tract. The expression of various apoptotic markers in the hepatic parenchyma, including CASPASE 3, CASPASE 8, BAX, FAS, FASL, GRANZYME B, and SURVIVIN, differed between YFV-positive cases and controls. Collectively, this study confirmed the complexity of YFV infection-induced apoptosis in situ. However, our data suggest that apoptosis in liver parenchyma lesions may significantly contribute to the pathogenesis of fatal YF in humans.<\/jats:p>","DOI":"10.3390\/v14061204","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T21:43:42Z","timestamp":1654119822000},"page":"1204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Factors Involved in the Apoptotic Cell Death Mechanism in Yellow Fever Hepatitis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7055-6851","authenticated-orcid":false,"given":"Jeferson","family":"da Costa Lopes","sequence":"first","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8391-2694","authenticated-orcid":false,"given":"Luiz F\u00e1bio Magno","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Pathology, State University of Para, Belem 66050-540, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9153-1234","authenticated-orcid":false,"given":"Arnaldo Jorge","family":"Martins Filho","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3085-566X","authenticated-orcid":false,"given":"Marcos Luiz Gaia","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio Cesar Henriques","family":"Mendes","sequence":"additional","affiliation":[{"name":"Department of Pathology, State University of Para, Belem 66050-540, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0546-0332","authenticated-orcid":false,"given":"F\u00e1bio Alves","family":"Ol\u00edmpio","sequence":"additional","affiliation":[{"name":"Tripical Medicine Unit, Federal University of Para, Belem 66075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1586-9887","authenticated-orcid":false,"given":"Vanessa","family":"do Socorro Cabral Miranda","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lais Carneiro","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6667-2796","authenticated-orcid":false,"given":"Jannifer Oliveira","family":"Chiang","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4607-9346","authenticated-orcid":false,"given":"Ana Cecilia Ribeiro","family":"Cruz","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Costa Alves","family":"Gal\u00facio","sequence":"additional","affiliation":[{"name":"Department of Pathology, State University of Para, Belem 66050-540, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1932-9976","authenticated-orcid":false,"given":"Raimunda","family":"do Socorro da Silva Azevedo","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia Caricio","family":"Martins","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-6701","authenticated-orcid":false,"given":"Maria Irma Seixas","family":"Duarte","sequence":"additional","affiliation":[{"name":"Schhol of Medicine, Sao Paulo University, Sao Paulo 05508-070, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge Rodrigues","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"},{"name":"Department of Pathology, State University of Para, Belem 66050-540, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6603-5527","authenticated-orcid":false,"given":"Pedro Fernando","family":"da Costa Vasconcelos","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil"},{"name":"Department of Pathology, State University of Para, Belem 66050-540, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6267-9966","authenticated-orcid":false,"given":"Juarez Ant\u00f4nio Sim\u00f5es","family":"Quaresma","sequence":"additional","affiliation":[{"name":"Department of Pathology, State University of Para, Belem 66050-540, Brazil"},{"name":"Tripical Medicine Unit, Federal University of Para, 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