GM-CSF Modulation of Zika Virus Infection in Neural and Epithelial Cells

Zika virus (ZIKV) is a neurotropic flavivirus associated with congenital microcephaly and neurological complications. This study investigated the modulatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on ZIKV infection in primary central nervous system (CNS) cell cultures from BALB/c mice and Vero epithelial cells. CNS cells were exposed to ZIKV and treated with GM-CSF, followed by analyses of morphological changes, cytokine and nitric oxide production, and Toll-like receptor (TLR) expression. ZIKV-infected astrocytes and microglia without inducing cytopathic effects but triggered reactive changes, including GFAP upregulation and microglial activation. GM-CSF enhanced the production of IL-6, TNF-α, and MCP-1 in CNS cultures but did not reduce ZIKV infection. In contrast, GM-CSF increased ZIKV infection and cytopathic effects in Vero cells, possibly by modulating the expression of receptors. Both ZIKV and GM-CSF upregulated TLR2 and TLR9, showing distinct temporal profiles across cell types. Nitric oxide levels remained undetectable under all conditions. These findings demonstrate a cell-type-dependent modulation of ZIKV infection by GM-CSF, with proinflammatory effects in glial cells and a permissive role in epithelial cells. The data suggest that GM-CSF, despite stimulating immune responses, may not offer antiviral protection and should be cautiously evaluated in the context of ZIKV infection.