Fig. 7

DENV 3 MG-20 and DENV 3 PV_BR infection models. DENV3 MG-20 was isolated from a fatal human case with CNS involvement, and this pathogenic behavior was reproduced in a mouse model, leading to animal death with CNS disease. When inoculated into human CNS cells (glioblastoma), it caused an intense cytopathic effect with endoplasmic hypertrophy, an intense flux of turgid vesicles with viruses and viral components leading to cell-to-cell fusion, syncytium, and cell death. We hypothesize that the neurovirulence of this virus is related to reduced titer in the extracellular environment and escape from the humoral response. In contrast, DENV3 PV_BR presented discrete CPE, as observed in TEM, on CNS cells but not leading to syncytium formation. Mice infected with DENV3 PV_BR did not have any signs of neurovirulence. We hypothesized that the balance between humoral and cytotoxic responses in this infection could impact the dissemination of the virus