Functional and immunological implications of dengue virus genotypes circulating in an endemic region of the state of São Paulo, Brazil

• Grant number: 23/15872-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2025
• End date: November 30, 2028
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Simone Kashima Haddad
• Grantee: Lucca Rocha Policastro
• Host Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
• Associated research grant: 21/11944-6 - Continuous improvement of vaccines: Center for Viral Surveillance and Serological Assessment (CeVIVAS), AP.CCD

Abstract

Dengue is an arbovirus that has a major impact in tropical regions, with a high incidence in Brazil. Although asymptomatic in many cases, it can have serious or even lethal manifestations. The dengue virus (DENV) presents itself as highly diverse serotypes, which are subdivided into genotypes. It is known that different serotypes vary in severity, infectivity and potential to cause epidemics. These variations also have an impact on the host immune response, especially to secondary infections, which is one of the major challenges for vaccine development. However, there are still gaps in the study of the singularities of each viral type, especially at genotype level. With this in mind, this project aims to functionally analyze the dengue virus genotypes isolated in the endemic region of Ribeirão Preto (SP) in terms of the immune response provoked in patients, the viral replication capacity and their pathogenicity in vitro. To this end, whole blood samples will be collected from symptomatic and asymptomatic individuals, which will undergo molecular diagnosis and genomic sequencing. The host immune response to each genotype will be assessed by quantifying cytokine levels in the samples and by immunophenotyping mononuclear cells. For tests on the characteristics of the virus, mononuclear cells from healthy individuals will be artificially infected with virions isolated from the samples of individuals with dengue. Viral replication will be analyzed by RT-qPCR and pathogenicity by the ratio between the percentage of infected cells and viable cells, determined by flow cytometry. With this, the project will not only study the diversity of viruses circulating in the region, but will also be able to elucidate issues of each serotype and genotype of DENV relevant to all endemic regions, since they have clinical and epidemiological consequences.