Morphological Aspects and Viremia Analysis of BALB/c Murine Model Experimentally Infected with Dengue Virus Serotype 4
Arthur da Costa Rasinhas,
Fernanda Cunha Jácome,
Gabriela Cardoso Caldas,
Ana Luisa Teixeira de Almeida,
Marcos Alexandre Nunes da Silva,
Daniel Dias Coutinho de Souza,
Amanda Carlos Paulino,
Derick Mendes Bandeira,
Raphael Leonardo,
Priscila Conrado Guerra Nunes,
Ronaldo Mohana-Borges,
Ortrud Monika Barth,
Flavia Barreto dos Santos,
Debora Ferreira Barreto Vieira
Affiliations
Arthur da Costa Rasinhas
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Fernanda Cunha Jácome
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Gabriela Cardoso Caldas
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Ana Luisa Teixeira de Almeida
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Marcos Alexandre Nunes da Silva
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Daniel Dias Coutinho de Souza
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Amanda Carlos Paulino
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Derick Mendes Bandeira
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Raphael Leonardo
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Priscila Conrado Guerra Nunes
Laboratory of Viral Immunology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Ronaldo Mohana-Borges
Laboratory of Biotechnology and Structural Bioengineering, Biophysics Institute Carlos Chagas Filho, Rio de Janeiro Federal University, Rio de Janeiro 21941-901, RJ, Brazil
Ortrud Monika Barth
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Flavia Barreto dos Santos
Laboratory of Viral Immunology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
Debora Ferreira Barreto Vieira
Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil
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.
