{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T09:17:38Z","timestamp":1764494258350,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Council for Scientific and Technological Development\u2014CNPq to PFCV","award":["401558\/2013-4","303999\/2016-0","CNPq and the National Institutes of Science and Technology: Emerging and re-emerging viruses\u2014INCT-VER","406360\/2022-7"],"award-info":[{"award-number":["401558\/2013-4","303999\/2016-0","CNPq and the National Institutes of Science and Technology: Emerging and re-emerging viruses\u2014INCT-VER","406360\/2022-7"]}]},{"name":"National Council for Scientific and Technological Development\u2014CNPq to PFCV","award":["401558\/2013-4","303999\/2016-0","CNPq and the National Institutes of Science and Technology: Emerging and re-emerging viruses\u2014INCT-VER","406360\/2022-7"],"award-info":[{"award-number":["401558\/2013-4","303999\/2016-0","CNPq and the National Institutes of Science and Technology: Emerging and re-emerging viruses\u2014INCT-VER","406360\/2022-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Non-human primates contribute to the spread of yellow fever virus (YFV) and the establishment of transmission cycles in endemic areas, such as Brazil. This study aims to investigate virological, histopathological and immunohistochemical findings in livers of squirrel monkeys (Saimiri spp.) infected with the YFV. Viremia occurred 1\u201330 days post infection (dpi) and the virus showed a predilection for the middle zone (Z2). The livers were jaundiced with subcapsular and hemorrhagic multifocal petechiae. Apoptosis, lytic and coagulative necrosis, steatosis and cellular edema were also observed. The immune response was characterized by the expression of S100, CD11b, CD57, CD4 and CD20; endothelial markers; stress and cell death; pro and anti-inflammatory cytokines, as well as Treg (IL-35) and IL-17 throughout the experimental period. Lesions during the severe phase of the disease were associated with excessive production of apoptotic pro-inflammatory cytokines, such as IFN-\u03b3 and TNF-\u03b1, released by inflammatory response cells (CD4+ and CD8+ T lymphocytes) and associated with high expression of molecules of adhesion in the inflammatory foci observed in Z2. Immunostaining of the local endothelium in vascular cells and the bile duct was intense, suggesting a fundamental role in liver damage and in the pathogenesis of the disease.<\/jats:p>","DOI":"10.3390\/v15020551","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T02:27:24Z","timestamp":1676600844000},"page":"551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Experimental Yellow Fever in Squirrel Monkey: Characterization of Liver In Situ Immune Response"],"prefix":"10.3390","volume":"15","author":[{"given":"Milene S.","family":"Ferreira","sequence":"first","affiliation":[{"name":"Evandro Chagas Institute, Rodovia BR 316, km-07, Ananindeua 67030-000, Par\u00e1, Brazil"},{"name":"Postgraduate Program in Biology of Infectious and Parasitic Agents, Federal University of Par\u00e1, Bel\u00e9m 66075-110, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge R.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institute, Rodovia BR 316, km-07, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-2999","authenticated-orcid":false,"given":"Pedro S.","family":"Bezerra J\u00fanior","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology, Institute of Veterinary Medicine, Federal University of Par\u00e1, Castanhal 68746-360, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1622-9849","authenticated-orcid":false,"given":"Val\u00edria D.","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology, Institute of Veterinary Medicine, Federal University of Par\u00e1, Castanhal 68746-360, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4369-5178","authenticated-orcid":false,"given":"Carlos A.","family":"Oliveira J\u00fanior","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology, Institute of Veterinary Medicine, Federal University of Par\u00e1, Castanhal 68746-360, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela R. C.","family":"Rivero","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Pathology, Institute of Veterinary Medicine, Federal University of Par\u00e1, Castanhal 68746-360, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo H. G.","family":"Castro","sequence":"additional","affiliation":[{"name":"National Primate Center, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilmara A.","family":"Silva","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institute, Rodovia BR 316, km-07, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Augusto P. C.","family":"Muniz","sequence":"additional","affiliation":[{"name":"National Primate Center, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliana V. P.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institute, Rodovia BR 316, km-07, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samir M. M.","family":"Casseb","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institute, Rodovia BR 316, km-07, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6210-6917","authenticated-orcid":false,"given":"Carla","family":"Pagliari","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Sao Paulo, Sao Paulo 01246-903, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9400-2036","authenticated-orcid":false,"given":"L\u00edvia C.","family":"Martins","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institute, Rodovia BR 316, km-07, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert B.","family":"Tesh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX 77555-0419, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6267-9966","authenticated-orcid":false,"given":"Juarez A. 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