Integrated analysis of the pathogenicity of Brazilian endemic Alphavirus and Orthoflavivirus in skeletal and cardiac muscle involvement

• Grant number: 25/07886-1
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Carla Torres Braconi dos Santos
• Grantee: Carla Torres Braconi dos Santos
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Alexandre Keiji Tashima ; Aparecida Sadae Tanaka ; Camila Malta Romano ; Katia da Conceição ; Marielton dos Passos Cunha ; Robert Andreata Santos

Abstract

Arboviruses comprise a group of viruses transmitted by arthropods, primarily characterized by viruses with RNA genomes. In tropical and subtropical regions, these viruses are responsible for emerging and re-emerging infectious diseases that constitute a major Public Health problem with economic and social impacts. Among the main viral agents responsible for epidemics, viruses from the Flaviviridae and Togaviridae families, from the Orthoflavivirus and Alphavirus genera, respectively, stand out. Epidemiologically, in Brazil, the highlights are the yellow fever virus (YFV), the Dengue virus (DENV), the Zika virus (ZIKV), the Chikungunya virus (CHIKV) and sporadic outbreaks related to the Mayaro virus (MAYV). These arboviruses are recognized for causing similar symptoms, with a clinical spectrum and diffuse symptoms, such as: disabling febrile syndromes, myalgia, exanthematic conditions and arthralgia. The pathogenicity related to this arbovirus can vary, affecting multiple organs, such as hepatic, renal, neurological, muscular, splenic, gastrointestinal and even ocular lesions. Furthermore, in severe cases, tissue damage is observed in cells of the skeletal and cardiac muscles, as well as in the pulmonary endothelium. In this sense, this project's main objective is to infer, determine and compare the pathogenicity patterns in infections caused by Alphavirus (CHIKV and MAYV) and Orthaflavivirus (DENV-2 and ZIKV) in human cellular models of immortalized skeletal muscle, cardiac muscle and endothelial somatic hybrid cell. This approach will allow us to evaluate in vitro infection in human cardiac iPS cells and thus understand the pathophysiological mechanisms of the arboviruses studied. Finally, the data obtained will be integrated regarding the expression of viral and cellular RNA, signaling pathways and common and divergent proteomic signatures specific to Orthoflavivirus and Alphavirus in a human cardiac model, which will help to find specific biomarkers for severe cases associated with mortality from arboviruses circulating in Brazil. (AU)