Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/11033
Title: Callithrix penicillata: a feasible experimental model for dengue virus infection.
Authors: Ferreira, Milene Silveira
Castro, Paulo Henrique Gomes de
Silva, Gilmara Abreu
Casseb, Samir Mansur Moraes
Dias Júnior, Antônio Gregório
Rodrigues, Sueli Guerreiros
Azevedo, Raimunda do Socorro da Silva
Silva, Matheus Fernandes Costa e
Zauli, Danielle Alves Gomes
Araújo, Márcio Sobreira Silva
Béla, Samantha Ribeiro
Carvalho, Andréa Teixeira
Martins Filho, Olindo Assis
Vasconcelos, Pedro Fernando da Costa
Affilliation: Fundação Oswaldo Cruz. Instituto Evandro Chagas. Ananindeua, PA, Brazil/Universidade Federal do Pará. Núcleo de Medicina Tropical. Belém, PA, Brazil
Centro Nacional de Primatas. Ananindeua, PA, Brazil
Centro Nacional de Primatas. Ananindeua, PA, Brazil
Fundação Oswaldo Cruz. Instituto Evandro Chagas. Ananindeua, PA, Brazil
Fundação Oswaldo Cruz. Instituto Evandro Chagas. Ananindeua, PA, Brazil
Fundação Oswaldo Cruz. Instituto Evandro Chagas. Ananindeua, PA, Brazil
Fundação Oswaldo Cruz. Instituto Evandro Chagas. Ananindeua, PA, Brazil
Fundacão Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoracão. Belo Horizonte, MG, Brazil
Fundacão Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoracão. Belo Horizonte, MG, Brazil
Fundacão Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoracão. Belo Horizonte, MG, Brazil
Fundacão Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoracão. Belo Horizonte, MG, Brazil
Fundacão Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoracão. Belo Horizonte, MG, Brazil
Fundacão Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoracão. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto Evandro Chagas. Ananindeua, PA, Brazil/Universidade do Estado do Pará. Belém, PA, Brazil
Abstract: 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-α, IL-2, IFN-γ, 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.
Keywords: Dengue virus infection
Experimental model
Immune response
Non-human
Primate
Issue Date: 2014
Publisher: Elsevier/North-Holland Biomedical Press
Citation: FERREIRA, Milene Silveira et al. Callithrix penicillata: a feasible experimental model for dengue virus infection. Immunol Lett., vo. 158, n. 1-2, p. 126-33, 2014
DOI: 10.1016/j.imlet.2013.12.008.
ISSN: 0165-2478
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos

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