Aedes aegypti salivary gland extract enhances Zika virus replication through immune modulation

BACKGROUND Mosquito saliva contains bioactive molecules that modulate host immunity and may influence arboviral infection. The contribution of Aedes aegypti salivary gland extract (SGE) to viral replication and immune regulation during Zika virus (ZIKV) infection remains poorly understood. OBJECTIVES To investigate the immunomodulatory effects of Ae. aegypti SGE during ZIKV infection. METHODS Peripheral blood mononuclear cells (PBMCs) and murine antigen-presenting cell lines were exposed to ZIKV with or without SGE. Viral replication was measured by quantitative polymerase chain reaction (qPCR), cell death and immune subsets by flow cytometry, oxidative stress markers by biochemical assays, and cytokine production by enzyme-linked immunosorbent assay (ELISA). FINDINGS SGE enhanced ZIKV replication, particularly in PBMCs, with increased RNA copies (median Δ = +1,779), reduced late apoptosis of CD4⁺ T cells (p = 0.0055), dendritic cell death (p 0.01), and impaired T-cell proliferation. SGE attenuated ZIKV-induced oxidative damage by restoring glutathione levels, reducing lipid and protein oxidation (p 0.001), and increasing nitric oxide (NO) production. Cytokine profiling revealed suppression of interferon-y (IFN-γ) (p 0.001) and induction of interleukin-4 (IL-4) (p 0.0001), indicating a Th2-skewed response. Murine cell lines confirmed SGE-driven cytokine modulation. MAIN CONCLUSIONS Ae. aegypti SGE alters host immune homeostasis, favouring ZIKV infection by weakening antiviral defences and redirecting immune and redox pathways, thereby facilitating viral expansion.