Impact of dengue virus infection in neurodegenerative processes associated with tauopathies

Dengue is an endemic disease in Argentina caused by DENV, whose impact on the central nervous system has gained relevance due to the increasing number of cases with neurological manifestations after infection. Tauopathies are neurodegenerative diseases associated with alterations in Tau protein, including mutations, changes in alternative splicing and post-translational modifications. DENV has been shown to alter alternative splicing in many transcripts. Therefore we hypothesize that DENV infection may affect Tau 3R/4R isoforms balance and promote pathological Tau accumulation. In this project we investigate the association between DENV infection and abnormal Tau metabolism. To this end, primary neurons derived from the htau mouse model were infected with DENV at DIV10. At 10, 20 and 30 days post infection Tau expression was evaluated by RT-qPCR and Western blot. So far, results suggest that DENV infection reduces Tau levels compared to non-infected neurons. Further analyses are ongoing to determine the time course of these changes. In parallel, we analyzed total Tau and p-Tau in cerebrospinal fluid (CSF) samples from individuals with past DENV infection by Western blot, to determine the conditions for this quantification. Together, this ongoing project explores the consequences of acute DENV infection in Tau metabolism, providing an initial framework to investigate the long-term impact of dengue exposure on Tau dynamics in human CSF.