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Evaluation of viral and host factors' contribuition to dengue pathogenesis

Grant number: 12/22606-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): March 01, 2013
Effective date (End): July 31, 2015
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Benedito Antônio Lopes da Fonseca
Grantee:Emiliana Pereira Abrão da Costa
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Dengue virus (DENV) infections result in the main disease transmitted by an arbovirus in the world and, due to its high prevalence in Brazil, are considered of major importance to the public health system of our country. The infection by any of the DENV induce a variety of clinical symptoms, ranging from asymptomatic infections to severe cases of the disease, called dengue hemorrhagic fever / dengue chock syndrome, including those involving the liver, heart or the CNS. The pathogenesis of the dengue infections is not completely understood, especially for the severe cases, where the immune response can play a double role either in protection or in the establishment of the severe cases. Besides that, the viral and the host characteristics are also important in the development of the severe cases, but their roles have not been clearly defined. Based on that, it becomes evident the sound relevance of understanding the molecular bases of dengue pathogenesis to contribute to the diagnosis, treatment and prevention of the disease; especially as a contribution to the development of protective vaccines against all four DENV serotypes. An important aspect of developing a dengue vaccine is the fact the it should avoid the increase in disease's severity due to a phenomenon known as "antibody enhancement of the disease".The present project is part of a broader project (FAPESP - Grant No. 2011/22514-0), entitled "Study of the viral, genetic and immunologic characteristics of the human host during the development of asymptomatic and severe cases of dengue", which aims to contribute to a better understanding of the pathophysiology of the disease, as the development of severe cases of this disease is related to a variety of different factors. The current project proposes to evaluate, in vitro, the viral and immunologic parameters related to dengue pathogenesis. The main goal is to investigate the correlation among the different clinical presentations of the disease to the virulence of the strains and the host's immune response, in a way to evaluate the contribution of each one of these factors to the development of the severe cases. To that, it will be investigated how the same virus strain behaves in cells from different patients (i.e. cells from patients presenting with different clinical manifestations), and also how the viruses originated from these patients will behave in different established cell lines. The study group will be composed of periphery blood monocytes (PBMC) from patients with symptoms of dengue fever (DF), dengue hemorrhagic fever (DHF), as well as asymptomatic patients. Each one of these cell groups will be infected with viruses isolated from patients with DF, DHF, and asymptomatics; as well as with prototype strains. It is noteworthy to say that up to the current date there are no similar reports in the literature that include the asymptomatic group and the experimental design above proposed. Thus, with this project, we believe that we might contribute to a more precise understanding of the molecular basis of dengue immunopathogenesis. (AU)