AUTHOR=Cavalcante Maria Sueli Barbosa , Santos Diego Siqueira , Araújo Lidineuza Machado , Freitas Priscilla Lieuthier , Silva Carlos Augusto Moreira , Carvalho Karina Glazianne Barbosa , Araújo Marialva Tereza Ferreira , Silva Eliana Viera Pinto da , Rodrigues de Farias Ana Paula Drummond , Guerreiro Diniz Daniel , Picanço Diniz Cristovam Wanderley , Diniz José Antonio Picanço 

TITLE=Inflammatory and neuropathological responses to Vesiculovirus carajas encephalitis in adult mice: variability, tolerance and resistance

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1499658

DOI=10.3389/fcimb.2025.1499658

ISSN=2235-2988

ABSTRACT=Vesiculovirus carajas (CARV) is a pathogen with neuroinvasive potential, yet its impact on neuroinflammation and sickness behavior remains poorly understood. In this study, we investigated the neuropathological and immunological responses to CARV encephalitis in adult BALB/c mice. Mice were intranasally inoculated with either infected or uninfected brain homogenates, and clinical, histopathological, and cytokine profiles were analyzed. CARV antigens were primarily detected in necrotic neurons, with prominent microglial activation near the ventricles and blood vessels. By day 10 post-infection, infected mice exhibited significantly elevated levels of MCP-1, IFN-γ, IL-12 p70, TNF-α, IL-6, and IL-10 in the brain, indicating a strong inflammatory response. These findings highlight the inflammatory modulation associated with CARV infection and suggest a hematogenous route of neuroinvasion, distinguishing CARV from other vesiculovirus species. This study provides new insights into the pathogenesis of CARV encephalitis and its potential impact on neuroimmune dynamics.