Nanotherapy approach to target ZIKA virus in microglia: A case study

Zika virus (ZIKV) specifically infects cells in the brain cortex, but it is unclear if astrocytes, brain microvascular endothelial cells, neurons, pericytes, and microglia can be infected by ZIKV. Additionally, the mechanisms that underlie the neuropathogenic effects of the ZIKV remain to be determined. ZIKV crosses the blood-brain barrier (BBB), which led us to examine the potential neurotoxic effects on microglia, which are the immune cells of the CNS. The current study examined the ability of ZIKV to infect HBMVEC, normal human astrocyte (NHA) and human microglia cells, and the effects of ZIKV on the expression of inflammatory cytokines and the immunomodulatory and antiviral effects of a curcumin-based silver nanoparticle (Cur-AgNP) nanoformulation on ZIKV-infected microglial cells in vitro. Additionally, our study examined the potential mechanisms that may underlie neuroinflammation associated with ZIKV infection that contributes to ZIKV-associated neuropathology. Our results indicate that the microglial cells are most susceptible to the ZIKV and the treatment of microglial cultures with the ZIKV resulted in a significant increase in inflammatory response as evident by the increased expression of proinflammatory cytokines. Further, the Cur-AgNP nanoformulation significantly reduced ZIKV expression in ZIKV-infected microglia and inhibited the expression of cytokines such as, IL-4, INF-γ, and IL-1β. The ZIKV activity was associated with increased apoptosis and oxidative stress, and treatment with Cur-AgNP reduced microglial apoptosis and decreased both reactive oxygen and nitric oxide species, thereby decreasing neuroinflammatory response. The Cur-AgNP nanoformulation could thus have clinical utility as a potential antiviral therapeutic in neuroinflammation associated with ZIKV infection.