INVESTIGATING THE POTENTIAL IMPACT OF ARBOVIRUS INFECTIONS ON HUMAN PANCREATIC BETA CELLS

• Grant number: 25/18857-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2025
• End date: November 30, 2028
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: José Luiz Proença Módena
• Grantee: Maressa Fernandes Bonfim
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The functional integrity of pancreatic beta cells is essential for maintaining glycaemic homeostasis and their dysfunction or loss is directly linked to the development of diabetes mellitus. Increasing evidence implicates viral infections as potential triggers of beta-cell injury and subsequent autoimmunity, particularly in type 1 diabetes, with enteroviruses such as coxsackie B viruses being the most studied. However, little is known about the direct or indirect effects of other viruses, including arboviruses endemic to Brazil, such as dengue virus (DENV), Zika virus (ZIKV), chikungunya virus (CHIKV), Mayaro virus (MAYV) and Oropouche virus (OROV) on beta-cell biology. Given the neurotropic potential of these viruses and the functional similarities between neurons and beta cells, this project aim to investigate whether DENV, ZIKV, CHIKV, MAYV and OROV can directly infect human beta cells and induce dysfunction, cell death or stress responses. The experimental strategy will integrate in vitro studies using human cell lines with in vivo approaches in mouse models. We will assess viral permissiveness, insulin secretion, endoplasmic reticulum stress, activation of innate immune pathways and the identification of host receptors involved in viral entry. A comparative transcriptomic analysis with neural cells will also be performed followed by in vivo validation through transplantation of human beta cells into immunodeficient mice and into spontaneous autoimmunity models (NOD). This work aims to uncover the metabolic consequences of arboviral infections, with a focus on the molecular mechanisms underlying pancreatic beta-cell dysfunction caused by viruses prevalent in the Brazilian population. The anticipated findings are expected to advance our understanding of post-viral metabolic complications and have direct implications for clinical management and translational diabetes research. (AU)