{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:09:38Z","timestamp":1777486178964,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordination for the Improvement of Higher Education Personnel (CAPES)","award":["88882.459701\/2019-01"],"award-info":[{"award-number":["88882.459701\/2019-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In the history of yellow fever (YF) outbreaks in Brazil, howler monkeys (Alouatta sp.) and marmosets (Callithrix sp.) have been among the most affected genera, exhibiting significant hepatic injuries similar to those seen in humans. However, limited information exists regarding yellow fever virus (YFV) infection in their central nervous system (CNS). To address this gap, an epidemiological study was conducted to assess tissue changes, viral detection, and cytokine profiles in the brains of both neotropical primate species when they are naturally infected with YFV. A total of 22 brain samples from these species (8 from Alouatta sp. and 14 from Callithrix sp.) showing infection with YFV in the liver via immunohistochemistry (IHC) were selected. From them, YFV antigen detection occurred in 35.7% (5\/14) of Callithrix sp. brain samples and 87.5% (7\/8) of Alouatta sp. samples, with a higher frequency of viral antigen quantification in Callithrix sp. Both species exhibited similar CNS lesions, characterized by congestion, low hemorrhage, limited inflammatory infiltration interstitial and perivascular edema associated with neuronal degeneration, neurophagy, and higher cell death (necrosis and apoptosis) quantification. Pro- and anti-inflammatory cytokine profiles were balanced, with TNF-\u03b1 and IL-1\u03b2 playing a key role in inflammation, while IL-10 and IL-13 exhibited a prominent role in immunomodulation, suggesting an anti-inflammatory modulation typical of flaviviruses occurs. This study demonstrates that YFV can induce CNS lesions in neotropical primates, establishing it as a secondary target of viral tropism. These findings highlight the importance of collecting nervous tissue during epizootics, particularly in Callithrix sp., as such tissue is often overlooked despite its critical role in disease monitoring.<\/jats:p>","DOI":"10.3390\/v17030386","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:22:52Z","timestamp":1741350172000},"page":"386","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Histopathological Changes and Immune Response Profile in the Brains of Non-Human Primates Naturally Infected with Yellow Fever Virus"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4077-7178","authenticated-orcid":false,"given":"Suzana Ribeiro de Melo","family":"Oliveira","sequence":"first","affiliation":[{"name":"Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ermelinda do Ros\u00e1rio Moutinho da","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelielma Garcia de Oliveira","family":"Prestes","sequence":"additional","affiliation":[{"name":"Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e1bio Silva","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marialva Tereza Ferreira","family":"de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orlando Pereira","family":"Amador Neto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria de Lourdes Gomes","family":"Lima","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca Nascimento","family":"de Alc\u00e2ntara","sequence":"additional","affiliation":[{"name":"Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3560-5499","authenticated-orcid":false,"given":"Daniel Damous","family":"Dias","sequence":"additional","affiliation":[{"name":"Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Rodrigues de","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9153-1234","authenticated-orcid":false,"given":"Arnaldo Jorge Martins","family":"Filho","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8578-9984","authenticated-orcid":false,"given":"Livia Medeiros Neves","family":"Casseb","sequence":"additional","affiliation":[{"name":"Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele Barbosa de Almeida","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Department of Arbovirology and Hemorrhagic Fevers, Evandro Chagas Institute, Rodovia BR-316 km 7 s\/n\u2014Levil\u00e2ndia, Ananindeua 67030-000, Par\u00e1, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/S1473-3099(16)30513-8","article-title":"Spread of Yellow Fever Virus Outbreak in Angola and the Democratic Republic of the Congo 2015\u201316: A Modelling Study","volume":"17","author":"Kraemer","year":"2017","journal-title":"Lancet Infect. 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