Author(s):
Ferreira, Milene Silveira ; Castro, Paulo Henrique Gomes de ; Silva, Gilmara Abreu ; Casseb, Samir Mansur Moraes ; Dias J?nior, Ant?nio Greg?rio ; Rodrigues, Sueli Guerreiro ; Azevedo, Raimunda do Socorro da Silva ; Silva, Matheus Fernandes Costa e ; Zauli, Danielle Alves Gomes ; Ara?jo, M?rcio Sobreira Silva ; B?la, Samantha Ribeiro ; Carvalho, Andr?a Teixeira ; Martins Filho, Olindo Assis ; Vasconcelos, Pedro Fernando da Costa
Date: 2020
Origin: Oasisbr
Subject(s): Primatas / anatomia & histologia; Callithrix / anatomia & histologia; V?rus da Dengue / imunologia; Dengue / complica??es; Anemia / etiologia; Modelos Animais de Doen?as; Biomarcadores / sangue; Estudos de Viabilidade; Carga Viral; Rea??o em Cadeia da Polimerase em Tempo Real / m?todos
Description
Funda??o Oswaldo Cruz (FIOCRUZ), Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq), Funda??o de Amparo ? Pesquisa de Minas Gerais (FAPEMIG); Instituto Nacional de Ci?ncia e Tecnologia para Febres Hemorr?gicas Virais (INCT-FHV grant CNPq/CAPES/FAPESPA 573739/2008-0).
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. N?cleo de Medicina Tropical. Bel?m, PA, Brazil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Centro Nacional de Primatas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Laborat?rio de Biomarcadores de Diagn?stico e Monitora??o. Belo Horizonte, MG, Brazil.
Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Laborat?rio de Biomarcadores de Diagn?stico e Monitora??o. Belo Horizonte, MG, Brazil.
Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Laborat?rio de Biomarcadores de Diagn?stico e Monitora??o. Belo Horizonte, MG, Brazil.
Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Laborat?rio de Biomarcadores de Diagn?stico e Monitora??o. Belo Horizonte, MG, Brazil.
Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Laborat?rio de Biomarcadores de Diagn?stico e Monitora??o. Belo Horizonte, MG, Brazil.
Funda??o Oswaldo Cruz. Centro de Pesquisas Ren? Rachou. Laborat?rio de Biomarcadores de Diagn?stico e Monitora??o. Belo Horizonte, MG, Brazil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade do Estado do Par?. Bel?m, PA, Brazil.
Although the murine models have the feasibility to reproduce some signs of dengue Virus (DENV) infection, the use of isogenic hosts with polarized immune response patterns does not reproduce the particularities of human disease. Our goal was to investigate the kinetics of peripheral blood biomarkers in immunocompetent Callithrix penicillata non-human primates subcutaneously infected with DENV-3. The viral load of infected animals was determinated by quantitative real time PCR. Measurements of DENV-3/IgM were performed, and several parameters were assessed by hemogram: red blood cells count, hemoglobin, hematocrit, white blood cells count, neutrophils, monocytes, lymphocytes, and platelets count. The coagulogram was performed by prothrombin time (PT), and activated partial thromboplastin time (APTT) assays. The renal function was monitored by urea and creatinine, and the liver function by the aspartate (AST), and alanine (ALT) aminotransferases. Also, the level of the cytokines IL-6, TNF-?, IL-2, IFN-?, IL-4 and IL-5 was quantified during the experimental study. Data analysis was performed considering relevant differences when baseline fold changes were found outside from 0.75 to 1.5 range. Our data demonstrated that infected animals presented relevant signs of dengue disease, including peaks of viremia at 5 days-post-infection (dpi), peaks of anti-DENV-3 IgM at 15 dpi and hemaglutination inhibition assay (HIA) from 15 to at 60 dpi. Despite early monocytosis, slight neutrophilia and lymphocytosis, animals developed persistent leucopenia starting at 4 dpi. Anemia episodes were steady at 3?4 dpi. Patent thrombocytopenia was observed from 1 to 15 dpi with sporadic decrease of APTT. A substantial increase of ALT and AST was observed with higher peak at 4 dpi. Moreover, early increases of TNF-alpha and IFN-gamma besides late increase of IFN-gamma were observed. The analysis of biomarkers network pointed out two relevant strong axes during early stages of dengue fever, a protective axes TNF-alpha/Lymphocytes/Platelets, and a pathological IL-2/IL-6/Viremia/Monocyte/PT bond. Later on, the biomarker network highlighted the interaction IFN-gamma/PLT/DENV-3(IgM;HAI)/PT, and the involvement of type-2 cytokines (IL-4; IL-5). Our findings demonstrated that C. penicillata is a feasible experimental model for dengue virus infection, which could be useful to pathogenesis studies, discovery of novel antiviral drugs as well as to evaluate vaccine candidates against DENV.
