{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T05:16:55Z","timestamp":1765948615045,"version":"3.48.0"},"reference-count":101,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institutes of Science and Technology: for Emerging and Reemerging Viruses","award":["CNPq 406360\/2022-7"],"award-info":[{"award-number":["CNPq 406360\/2022-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>This study evaluated hepatic pathological and phenotypic alterations, along with the inflammatory response, following sequential dengue virus (DENV) infection in Callithrix penicillata, a relevant model for human endemic scenarios. Twenty-six animals were initially infected subcutaneously with DENV-3. Thirteen were euthanized between 1 and 7 days post-infection (dpi) to assess the acute phase, and up to 60 dpi for the convalescent phase. The remaining animals received a secondary DENV-2 infection two months later. Liver samples underwent histopathological and immunohistochemical analysis. Viral antigens were identified in hepatocytes, Kupffer cells, and Councilman bodies. Observed liver changes included apoptosis, lytic necrosis, midzonal inflammation, Kupffer cell hyperplasia and hypertrophy, sinusoidal dilation, and hemosiderin deposition. Both primary and secondary infections increased activated macrophages, NK cells, S-100 protein, and B lymphocytes. Primary infection was associated with elevated CD4+ T cells, IFN-\u03b3, TGF-\u03b2, IL-10, and Fas expression, whereas secondary infection induced higher IFN-\u03b3, TNF-\u03b1, IL-8, Fas, and VCAM levels. These findings mirror hepatic alterations in severe human dengue cases and underscore the role of direct viral effects and immune dysregulation in liver injury. The results support C. penicillata as a suitable non-human primate model for studying DENV pathogenesis.<\/jats:p>","DOI":"10.3390\/v17121619","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:32:37Z","timestamp":1765805557000},"page":"1619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequential Dengue Virus Infection in Marmosets: Histopathological and Immune Responses in the Liver"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9576-6620","authenticated-orcid":false,"given":"Daniele Freitas","family":"Henriques","sequence":"first","affiliation":[{"name":"Department of Arboviruses and Hemorrhagic Fevers, Evandro Chagas Institute, Ananindeua 67030-000, Brazil"},{"name":"Postgraduate Program in Biology of Infectious and Parasitic Agents, Federal University of Par\u00e1, Bel\u00e9m 66075-110, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8578-9984","authenticated-orcid":false,"given":"Livia M. N.","family":"Casseb","sequence":"additional","affiliation":[{"name":"Department of Arboviruses and Hemorrhagic Fevers, Evandro Chagas Institute, Ananindeua 67030-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milene S.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Center of Tropical Medicine, Federal University of Par\u00e1, Bel\u00e9m 66055-240, Brazil"},{"name":"State University of Par\u00e1, Bel\u00e9m 66050-540, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa S.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Center of Tropical Medicine, Federal University of Par\u00e1, Bel\u00e9m 66055-240, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hellen T.","family":"Fuzii","sequence":"additional","affiliation":[{"name":"Center of Tropical Medicine, Federal University of Par\u00e1, Bel\u00e9m 66055-240, 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, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciane","family":"Kanashiro","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo H. 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J. Health Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e88","DOI":"10.1016\/S1473-3099(16)30473-X","article-title":"Dengue: Knowledge gaps, unmet needs, and research priorities","volume":"17","author":"Katzelnick","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"taab146","DOI":"10.1093\/jtm\/taab146","article-title":"Global burden for dengue and the evolving pattern in the past 30 years","volume":"28","author":"Yang","year":"2021","journal-title":"J. Travel Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s40471-017-0095-y","article-title":"A New Look at an Old Disease: Recent Insights into the Global Epidemiology of Dengue","volume":"4","author":"Sharp","year":"2017","journal-title":"Curr. Epidemiol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hamel, R., Surasombatpattana, P., Wichit, S., Dauv\u00e9, A., Donato, C., Pompon, J., Vijaykrishna, D., Liegeois, F., Vargas, R.M., and Luplertlop, N. (2019). Phylogenetic analysis revealed the co-circulation of four dengue virus serotypes in Southern Thailand. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221179"},{"key":"ref_6","first-page":"46","article-title":"Co-circulation of all the Four Serotype of Dengue Virus in Endemic Region of Saurashtra, Gujarat during 2019-2020 Season","volume":"15","author":"Aring","year":"2021","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1099\/0022-1317-70-1-37","article-title":"Antigenic Relationships between Flaviviruses as Determined by Cross-neutralization Tests with Polyclonal Antisera","volume":"70","author":"Calisher","year":"1989","journal-title":"J. Gen. Virol."},{"key":"ref_8","unstructured":"World Health Organization (2009). Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control, WHO. Available online: https:\/\/www.paho.org\/sites\/default\/files\/2022-08\/2009-cde-dengue-guidelines-diagnosis-treatment-prevention-control.pdf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4269\/ajtmh.2003.68.191","article-title":"Serotype-specific dengue virus circulation and dengue disease in bangkok, thailand from 1973 to 1999","volume":"68","author":"Nisalak","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/0035-9203(68)90120-X","article-title":"Dengue haemorrhagic fever: A pathological study","volume":"62","author":"Burke","year":"1968","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.4269\/ajtmh.1983.32.1108","article-title":"Transovarial Transmission of Dengue Viruses by Mosquitoes: Aedes albopictus and Aedes aegypti","volume":"32","author":"Rosen","year":"1983","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1086\/383043","article-title":"Localization of Dengue Virus in Naturally Infected Human Tissues, by Immunohistochemistry and In Situ Hybridization","volume":"189","author":"Jessie","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1038\/labinvest.2009.83","article-title":"Hepatic damage associated with dengue-2 virus replication in liver cells of BALB\/c mice","volume":"89","author":"Paes","year":"2009","journal-title":"Lab. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/INF.0b013e3181bc3c5b","article-title":"Heart and Skeletal Muscle Are Targets of Dengue Virus Infection","volume":"29","author":"Salgado","year":"2010","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"P\u00f3voa, T.F., Alves, A.M.B., Oliveira, C.A.B., Nuovo, G.J., Chagas, V.L.A., and Paes, M.V. (2014). The Pathology of Severe Dengue in Multiple Organs of Human Fatal Cases: Histopathology, Ultrastructure and Virus Replication. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0083386"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"P\u00f3voa, T.F., Oliveira, E.R.A., Bas\u00edlio-De-Oliveira, C.A., Nuovo, G.J., Chagas, V.L.A., Salom\u00e3o, N.G., Mota, E.M., and Paes, M.V. (2016). Peripheral Organs of Dengue Fatal Cases Present Strong Pro-Inflammatory Response with Participation of IFN-Gamma-, TNF-Alpha- and RANTES-Producing Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168973"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1111\/trf.15416","article-title":"Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells","volume":"59","author":"Hsu","year":"2019","journal-title":"Transfusion"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1016\/j.ajpath.2013.02.027","article-title":"Inflammatory and innate immune responses in dengue infection: Protection versus disease induction","volume":"182","author":"Costa","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/imm.12188","article-title":"Dengue virus infection: Current concepts in immune mechanisms and lessons from murine models","volume":"141","author":"Guabiraba","year":"2014","journal-title":"Immunology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1002\/jmv.23758","article-title":"Immunopathogenesis of dengue hemorrhagic fever: Contribution to the study of human liver lesions","volume":"86","author":"Pagliari","year":"2013","journal-title":"J. Med. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S137","DOI":"10.29271\/jcpsp.2018.06.S137","article-title":"Postmortem Findings In Fatal Dengue Haemorrhagic Fever","volume":"28","author":"Ahsan","year":"2018","journal-title":"J. Coll. Physicians Surg. Pak."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Khanam, A., Guti\u00e9rrez-Barbosa, H., Lyke, K.E., and Chua, J.V. (2022). Immune-Mediated Pathogenesis in Dengue Virus Infection. Viruses, 14.","DOI":"10.3390\/v14112575"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yong, Y.K., Wong, W.F., Vignesh, R., Chattopadhyay, I., Velu, V., Tan, H.Y., Zhang, Y., Larsson, M., and Shankar, E.M. (2022). Dengue Infection\u2014Recent Advances in Disease Pathogenesis in the Era of COVID-19. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.889196"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4269\/ajtmh.23-0545","article-title":"Dengue virus infection: Immune response and thera-peutic targets","volume":"112","author":"Tin","year":"2025","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1086\/315072","article-title":"Early CD69 Expression on Peripheral Blood Lymphocytes from Children with Dengue Hemorrhagic Fever","volume":"180","author":"Green","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Weg, C.A.M.V.D., Pannuti, C.S., De Ara\u00fajo, E.S.A., Ham, H.-J.V.D., Andeweg, A.C., Boas, L.S.V., Felix, A.C., Carvalho, K.I., De Matos, A.M., and Levi, J.E. (2013). Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease. PLoS Neglected Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002236"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sol\u00f3rzano, V.E.F., Faria, N.R.d.C., dos Santos, C.F., Corr\u00eaa, G., Cipitelli, M.d.C., Ribeiro, M.D., de Souza, L.J., Damasco, P.V., da Cunha, R.V., and dos Santos, F.B. (2021). Different Profiles of Cytokines, Chemokines and Coagulation Mediators Associated with Severity in Brazilian Patients Infected with Dengue Virus. Viruses, 13.","DOI":"10.3390\/v13091789"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ijmmb.2022.01.010","article-title":"Pathophysiologic and Prognostic Role of Proinflammatory and Regulatory Cytokines in Dengue Fever","volume":"4","author":"Iyer","year":"2022","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1093\/infdis\/jiac273","article-title":"The Cytokines CXCL10 and CCL2 and the Kynurenine Metabolite Anthranilic Acid Accurately Predict Patients at Risk of Developing Dengue With Warning Signs","volume":"226","author":"Jusof","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1086\/517807","article-title":"Pathophysiologic and Prognostic Role of Cytokines in Dengue Hemorrhagic Fever","volume":"177","author":"Bethell","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bozza, F.A., Cruz, O.G., Zagne, S.M., Azeredo, E.L., Nogueira, R.M., Assis, E.F., Bozza, P.T., and Kubelka, C.F. (2008). Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity. BMC Infect. Dis., 8.","DOI":"10.1186\/1471-2334-8-86"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1096\/fj.09-139469","article-title":"Contribution of Macrophage Mi-gration Inhibitory Factor to the Pathogenesis of Dengue Virus Infection","volume":"24","author":"Amaral","year":"2010","journal-title":"FASEB J."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"De-Oliveira-Pinto, L.M., Marinho, C.F., Povoa, T.F., De Azeredo, E.L., De Souza, L.A., Barbosa, L.D.R., Motta-Castro, A.R.C., Alves, A.M.B., \u00c1vila, C.A.L., and De Souza, L.J. (2012). Regulation of Inflammatory Chemokine Receptors on Blood T Cells Associated to the Circulating Versus Liver Chemokines in Dengue Fever. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038527"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Patro, A.R.K., Mohanty, S., Prusty, B.K., Singh, D.K., Gaikwad, S., Saswat, T., Chattopadhyay, S., Das, B.K., Tripathy, R., and Ravindran, B. (2019). Cytokine Signature Associated with Disease Severity in Dengue. Viruses, 11.","DOI":"10.3390\/v11010034"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Puc, I., Ho, T.-C., Yen, K.-L., Vats, A., Tsai, J.-J., Chen, P.-L., Chien, Y.-W., Lo, Y.-C., and Perng, G.C. (2021). Cytokine Signature of Dengue Patients at Different Severity of the Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062879"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"199306","DOI":"10.1016\/j.virusres.2023.199306","article-title":"Temporal cytokine storm dynamics in dengue infection predicts severity","volume":"341","author":"Bhatt","year":"2024","journal-title":"Virus Res."},{"key":"ref_37","unstructured":"Bhamarapravati, N. (1993). Pathology of Dengue Haemorrhagic Fever. Monograph on Dengue\/Dengue Hemorrhagic Fever, World Health Organization."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3390\/v4010062","article-title":"Animal Models of Dengue Virus Infection","volume":"4","author":"Zompi","year":"2012","journal-title":"Viruses"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00705-021-05298-2","article-title":"Mammalian animal models for dengue virus infection: A recent overview","volume":"167","author":"Kayesh","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Coronel-Ruiz, C., Guti\u00e9rrez-Barbosa, H., Medina-Moreno, S., Velandia-Romero, M.L., Chua, J.V., Castellanos, J.E., and Zapata, J.C. (2020). Humanized Mice in Dengue Research: A Comparison with Other Mouse Models. Vaccines, 8.","DOI":"10.3390\/vaccines8010039"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/S0966-842X(01)02288-0","article-title":"Epidemic dengue\/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century","volume":"10","author":"Gubler","year":"2002","journal-title":"Trends Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Azami, N.A.M., Takasaki, T., Kurane, I., and Moi, M.L. (2020). Non-Human Primate Models of Dengue Virus Infection: A Comparison of Viremia Levels and Antibody Responses during Primary and Secondary Infection among Old World and New World Monkeys. Pathogens, 9.","DOI":"10.3390\/pathogens9040247"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/nrmicro2595","article-title":"Fever from the forest: Prospects for the continued emergence of sylvatic dengue virus and its impact on public health","volume":"9","author":"Vasilakis","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1182\/blood-2009-09-242990","article-title":"Dengue virus\u2013induced hemorrhage in a nonhuman primate model","volume":"115","author":"Onlamoon","year":"2010","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1099\/vir.0.031229-0","article-title":"Common marmoset (Callithrix jacchus) as a primate model of dengue virus infection: Development of high levels of viraemia and demonstration of protective immunity","volume":"92","author":"Omatsu","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1600-0684.2012.00552.x","article-title":"Changes in hematological and serum biochemical parameters in common marmosets (Callithrix jacchus) after inoculation with dengue virus","volume":"41","author":"Omatsu","year":"2012","journal-title":"J. Med. Primatol."},{"key":"ref_47","first-page":"484","article-title":"Diagn\u00f3stico de Febre Hemorr\u00e1gica em Primata N\u00e3o Humano Causado pelo V\u00edrus Dengue: Relato de Caso","volume":"42","author":"Costa","year":"2009","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.imlet.2013.12.008","article-title":"Callithrix penicillata: A feasible experimental model for dengue virus infection","volume":"158","author":"Ferreira","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4977","DOI":"10.1128\/JCM.43.10.4977-4983.2005","article-title":"Serotype-Specific Detection of Dengue Viruses in a Fourplex Real-Time Reverse Transcriptase PCR Assay","volume":"43","author":"Johnson","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1099\/0022-1317-40-3-531","article-title":"Isolation of a Singh\u2019s Aedes albopictus Cell Clone Sensitive to Dengue and Chikungunya Viruses","volume":"40","author":"Igarashi","year":"1978","journal-title":"J. Gen. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4269\/ajtmh.1984.33.158","article-title":"Mosquito Cell Cultures and Specific Monoclonal Antibodies in Surveillance for Dengue Viruses","volume":"33","author":"Gubler","year":"1984","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_52","unstructured":"Ferreira, M.S. (2012). Estudo Experimental sobre a Resposta Imunol\u00f3gica em Infec\u00e7\u00f5es Sequenciais pelo V\u00edrus Dengue 3 e pelo V\u00edrus Dengue 2 em Primatas N\u00e3o Humanos da Esp\u00e9cie Callithrix Penicillata, Universidade Federal do Par\u00e1."},{"key":"ref_53","unstructured":"Travassos da Rosa, A.P.A., Travassos da Rosa, E.S., Travassos da Rosa, J.F.S., D\u00e9gallier, N., Vasconcelos, P.F.C., Rodrigues, S.G., and Cruz, A.C.R. (1994). Os Arbov\u00edrus no Brasil: Generalidades, M\u00e9todos e T\u00e9cnicas de Estudo; Documento T\u00e9cnico n\u00ba 2, Instituto Evandro Chagas\/Funda\u00e7\u00e3o Nacional de Sa\u00fade."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"408","DOI":"10.4269\/ajtmh.1991.45.408","article-title":"Demonstration of Yellow Fever and Dengue Antigens in Formalin-Fixed Paraffin-Embedded Human Liver by Immunohistochemical Analysis","volume":"45","author":"Hall","year":"1991","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.actatropica.2005.03.003","article-title":"Reconsideration of histopathology and ultrastructural aspects of the human liver in yellow fever","volume":"94","author":"Quaresma","year":"2005","journal-title":"Acta Trop."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","article-title":"Histological grading and staging of chronic hepatitis","volume":"22","author":"Ishak","year":"1995","journal-title":"J. Hepatol."},{"key":"ref_57","unstructured":"Anthony, P.P., Ishak, K.G., Nayak, N.C., Poulsen, H.E., Scheuer, P.J., and Sobin, L.H. (1977). The Morphology of Acute Hepatitis, World Health Organization."},{"key":"ref_58","unstructured":"MacSween, R.N.M., Burt, A.D., Portmann, B., H\u00fcbscher, S., Ferrell, L., and Schmid, M. (2012). MacSween\u2019s Pathology of the Liver, Elsevier. [6th ed.]."},{"key":"ref_59","unstructured":"Burt, A.D., Ferrell, L.D., and H\u00fcbscher, S.G. (2018). Morphology of the Liver, Cambridge University Press. [1st ed.]."},{"key":"ref_60","unstructured":"Lefkowitch, J.H. (2015). Anatomic Pathology of the Liver, Elsevier. [2nd ed.]."},{"key":"ref_61","unstructured":"Dancey, C., and Reidy, J. (2006). Statistics Without Mathematics for Psychology: Using SPSS for Windows, Artmed."},{"key":"ref_62","first-page":"2380","article-title":"Serosurvey of Arbovirus in Free-Living Non-Human Primates (Sapajus spp.) in Brazil","volume":"2","author":"Batista","year":"2015","journal-title":"J. Environ. Anal. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1080\/00034983.1967.11686519","article-title":"Pathology of Thailand haemorrhagic fever: A study of 100 autopsy cases","volume":"61","author":"Bhamarapravati","year":"1967","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s004280000329","article-title":"Liver Histopathology and Biological Correlates in Five Cases of Fatal Dengue Fever in Vietnamese Children","volume":"438","author":"Huerre","year":"2001","journal-title":"Virchows Arch."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.humpath.2014.01.022","article-title":"Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar","volume":"45","author":"Aye","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Moragas, L.J., Alves, F.d.A.V., Oliveira, L.d.L.S., Salom\u00e3o, N.G., Azevedo, C.G., da Silva, J.F.R., Bas\u00edlio-De-Oliveira, C.A., Bas\u00edlio-De-Oliveira, R., Mohana-Borges, R., and de Carvalho, J.J. (2023). Liver immunopathogenesis in fatal cases of dengue in children: Detection of viral antigen, cytokine profile and inflammatory mediators. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1215730"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ribeiro, Y.P., Falc\u00e3o, L.F.M., Smith, V.C., de Sousa, J.R., Pagliari, C., Franco, E.C.S., Cruz, A.C.R., Chiang, J.O., Martins, L.C., and Nunes, J.A.L. (2023). Comparative Analysis of Human Hepatic Lesions in Dengue, Yellow Fever, and Chikungunya: Revisiting Histopathological Changes in the Light of Modern Knowledge of Cell Pathology. Pathogens, 12.","DOI":"10.3390\/pathogens12050680"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.17554\/j.issn.2224-3992.2019.07.823","article-title":"Dengue Virus and Yellow Fever Virus Damage the Liver: A Systematic Review About the Histopathological Profiles","volume":"8","author":"Costa","year":"2019","journal-title":"J. Gastroenterol. Hepatol. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/S0046-8177(99)90230-7","article-title":"Report of a fatal case of dengue infection with hepatitis: Demonstration of dengue antigens in hepatocytes and liver apoptosis","volume":"30","author":"Couvelard","year":"1999","journal-title":"Hum. Pathol."},{"key":"ref_70","unstructured":"Torres, E.M. (2005). Dengue, Fiocruz. Available online: https:\/\/fiocruz.br\/livro\/dengue."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6353","DOI":"10.1128\/MCB.18.11.6353","article-title":"The Mitochondrial Permeability Transition Is Required for Tumor Necrosis Factor Alpha-Mediated Apoptosis and Cytochrome c Release","volume":"18","author":"Bradham","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1126\/science.1071809","article-title":"Signal Transduction by the TGF-\u03b2 Superfamily","volume":"296","author":"Attisano","year":"2002","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0969-2126(01)00702-X","article-title":"Phosphoserine-Dependent Regulation of Protein-Protein Interactions in the Smad Pathway","volume":"10","author":"Wrana","year":"2002","journal-title":"Structure"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.virol.2005.09.058","article-title":"Revisiting the liver in human yellow fever: Virus-induced apoptosis in hepatocytes associated with TGF-\u03b2, TNF-\u03b1 and NK cells activity","volume":"345","author":"Quaresma","year":"2006","journal-title":"Virology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.humimm.2010.08.004","article-title":"Tumor necrosis factor\u2013alpha, transforming growth factor\u2013\u03b21, and interleukin-10 gene polymorphisms: Implication in protection or susceptibility to dengue hemorrhagic fever","volume":"71","author":"Perez","year":"2010","journal-title":"Hum. Immunol."},{"key":"ref_76","unstructured":"Abbas, A.K., Lichtman, A.H., and Pillai, S. (2023). Imunologia Celular e Molecular, Guanabara Koogan. [10th ed.]."},{"key":"ref_77","unstructured":"Santos, N.S.O., Romanos, M.T.V., and Wigg, M.D. (2008). Introdu\u00e7\u00e3o \u00e0 Virologia Humana, Guanabara Koogan. [2nd ed.]."},{"key":"ref_78","first-page":"39","article-title":"Noninvasive diagnosis of liver fibrosis in patients with chronic hepatitis C","volume":"7","author":"Castera","year":"2005","journal-title":"Medscape Gen. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.cld.2004.06.007","article-title":"Hepatitis C and steatosis","volume":"8","author":"Dev","year":"2004","journal-title":"Clin. Liver Dis."},{"key":"ref_80","unstructured":"Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2002). Molecular Biology of the Cell, Garland Science. [4th ed.]."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1590\/S0074-02762006000800014","article-title":"Morphological studies in a model for dengue-2 virus infection in mice","volume":"101","author":"Barth","year":"2006","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0923-2516(97)88364-1","article-title":"The impact of dengue haemorrhagic fever on liver function","volume":"148","author":"Nguyen","year":"1997","journal-title":"Res. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1590\/S1413-86702007000400007","article-title":"The impact of dengue on liver function as evaluated by aminotransferase levels","volume":"11","author":"Nogueira","year":"2007","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1590\/S0037-86822011005000061","article-title":"Clinical and laboratory findings in patients with dengue associated with hepatopathy","volume":"44","author":"Nascimento","year":"2011","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"265","DOI":"10.4269\/ajtmh.1992.47.265","article-title":"Liver Biochemical Tests and Dengue Fever","volume":"47","author":"Kuo","year":"1992","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Lee, L.K., Gan, V.C., Lee, V.J., Tan, A.S., Leo, Y.S., and Lye, D.C. (2012). Clinical relevance and discriminatory value of elevated liver ami-notransferase levels for dengue severity. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001676"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.actatropica.2015.12.013","article-title":"Evaluation of aminotransferase abnormality in dengue patients: A meta analysis","volume":"156","author":"Wang","year":"2016","journal-title":"Acta Trop."},{"key":"ref_88","unstructured":"Brasil, R.A. (2005). Caracteriza\u00e7\u00e3o do Fen\u00f3tipo da Resposta Inflamat\u00f3ria, da Express\u00e3o de Citocinas e do Mecanismo de Morte Celular no F\u00edgado de Pacientes com Febre Hemorr\u00e1gica da Dengue, Universidade de S\u00e3o Paulo."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1152\/physrev.1989.69.3.708","article-title":"Functional specialization of different hepatocyte populations","volume":"69","author":"Jungermann","year":"1989","journal-title":"Physiol. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"6209","DOI":"10.4049\/jimmunol.170.12.6209","article-title":"Fas (CD95) Induces Proinflammatory Cytokine Responses by Human Monocytes and Monocyte-Derived Macrophages","volume":"170","author":"Park","year":"2003","journal-title":"J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/nature20138","article-title":"Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs","volume":"539","author":"Cummings","year":"2016","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.trstmh.2006.02.019","article-title":"Hepatocyte lesions and cellular immune response in yellow fever infection","volume":"101","author":"Quaresma","year":"2007","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/rmv.1752","article-title":"Immunity and immune response, pathology and pathologic changes: Progress and challenges in the immunopathology of yellow fever","volume":"23","author":"Quaresma","year":"2013","journal-title":"Rev. Med Virol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/BF01310705","article-title":"Dengue-2 virus infection of human mononuclear cell lines and establishment of persistent infections","volume":"110","author":"Kurane","year":"1990","journal-title":"Arch. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.4049\/jimmunol.164.12.6480","article-title":"NK Cells Cause Liver Injury and Facilitate the Induction of T Cell-Mediated Immunity to a Viral Liver Infection","volume":"164","author":"Liu","year":"2000","journal-title":"J. Immunol."},{"key":"ref_96","unstructured":"Scroferneker, M.L., and Pohlmann, P.R. (1998). Imunologia: B\u00e1sica e Aplicada, Sagra Luzzatto."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/1096-9071(200103)63:3<247::AID-JMV1008>3.0.CO;2-F","article-title":"Activation of coagulation and fibrinolysis during dengue virus infection","volume":"63","author":"Huang","year":"2001","journal-title":"J. Med. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/emi.2015.24","article-title":"Serum levels of soluble vascular cell adhesion molecules may correlate with the severity of dengue virus-1 infection in adults","volume":"4","author":"Liao","year":"2015","journal-title":"Emerg. Microbes Infect."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"6829","DOI":"10.1128\/jvi.66.11.6829-6835.1992","article-title":"Baculovirus gp64 Envelope Glycoprotein Is Sufficient To Mediate pH-Dependent Membrane Fusion","volume":"66","author":"Blissard","year":"1992","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"186","DOI":"10.7883\/yoken.JJID.2016.123","article-title":"Synergistic Effect of TNF-\u03b1 and Dengue Virus Infection on Adhesion Molecule Reorganization in Human Endothelial Cells","volume":"70","author":"Inyoo","year":"2017","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/1096-9071(20000201)63:2<150::AID-JMV1010>3.0.CO;2-A","article-title":"Antibody-dependent enhancement of heterotypic dengue infections involved in suppression of IFN-\u03b3 production","volume":"63","author":"Yang","year":"2001","journal-title":"J. Med. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/12\/1619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T05:12:03Z","timestamp":1765948323000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/12\/1619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,15]]},"references-count":101,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["v17121619"],"URL":"https:\/\/doi.org\/10.3390\/v17121619","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2025,12,15]]}}}