{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:24:30Z","timestamp":1760235870301,"version":"build-2065373602"},"reference-count":95,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"publisher","award":["IOC-023-FIO-18-2-58"],"award-info":[{"award-number":["IOC-023-FIO-18-2-58"]}],"id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/202.003\/2016"],"award-info":[{"award-number":["E-26\/202.003\/2016"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["302462\/2018-0","301992\/2017-7"],"award-info":[{"award-number":["302462\/2018-0","301992\/2017-7"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Ever since its brief introduction in the Brazilian territory in 1981, dengue virus serotype 4 (DENV-4) remained absent from the national epidemiological scenario for almost 25 years. The emergence of DENV-4 in 2010 resulted in epidemics in most Brazilian states. DENV-4, however, remains one of the least studied among the four DENV serotypes. Despite being known as a mild serotype, DENV-4 is associated with severe cases and deaths and deserves to be investigated; however, the lack of suitable experimental animal models is a limiting factor for pathogenesis studies. Here, we aimed to investigate the susceptibility and potential tropism of DENV-4 for liver, lung and heart of an immunocompetent mice model, and to evaluate and investigate the resulting morphological and ultrastructural alterations upon viral infection. BALB\/c mice were inoculated intravenously with non-neuroadapted doses of DENV-4 isolated from a human case. The histopathological analysis of liver revealed typical alterations of DENV, such as microsteatosis, edema and vascular congestion, while in lung, widespread areas of hemorrhage and interstitial pneumonia were observed. While milder alterations were present in heart, characterized by limited hemorrhage and discrete presence of inflammatory infiltrate, the disorganization of the structure of the intercalated disc is of particular interest. DENV-4 RNA was detected in liver, lung, heart and serum of BALB\/c mice through qRT-PCR, while the NS3 viral protein was observed in all of the aforementioned organs through immunohistochemistry. These findings indicate the susceptibility of the model to the serotype and further reinforce the usefulness of BALB\/c mice in studying the many alterations caused by DENV.<\/jats:p>","DOI":"10.3390\/v13101954","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:59:47Z","timestamp":1633917587000},"page":"1954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Morphological Aspects and Viremia Analysis of BALB\/c Murine Model Experimentally Infected with Dengue Virus Serotype 4"],"prefix":"10.3390","volume":"13","author":[{"given":"Arthur","family":"da Costa Rasinhas","sequence":"first","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Cunha J\u00e1come","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Cardoso Caldas","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2189-7115","authenticated-orcid":false,"given":"Ana Luisa","family":"Teixeira de Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos Alexandre","family":"Nunes da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Dias Coutinho de Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Carlos Paulino","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6591-4987","authenticated-orcid":false,"given":"Derick","family":"Mendes Bandeira","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Leonardo","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4841-9308","authenticated-orcid":false,"given":"Priscila","family":"Conrado Guerra Nunes","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronaldo","family":"Mohana-Borges","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology and Structural Bioengineering, Biophysics Institute Carlos Chagas Filho, Rio de Janeiro Federal University, Rio de Janeiro 21941-901, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2418-8605","authenticated-orcid":false,"given":"Ortrud","family":"Monika Barth","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1309-5366","authenticated-orcid":false,"given":"Flavia","family":"Barreto dos Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Immunology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1014-0755","authenticated-orcid":false,"given":"Debora","family":"Ferreira Barreto Vieira","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S1473-3099(16)00026-8","article-title":"The global burden of dengue: An analysis from the Global Burden of Disease Study 2013","volume":"16","author":"Stanaway","year":"2016","journal-title":"Lancet Infect. 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