<p class="first" id="P2">Zika virus (ZIKV) is a mosquito-borne flavivirus associated
neonatal birth defects, but the causative mechanism is incompletely understood.
ZIKV shares sequence homology and early clinical manifestations with yellow
fever virus (YFV) and dengue virus (DENV) and are all transmitted in urban
cycles by the same species of mosquitoes. However, YFV and DENV have been rarely
reported to cause congenital diseases. Here, we compared infection with a
contemporary ZIKV strain (FSS13025) to YFV17D and DENV-4 in human monocytic
cells (THP-1) and first-trimester trophoblasts (HTR-8). Our results suggest that
all three viruses have similar tropisms for both cells. Nevertheless, ZIKV
induced strong type 1 IFN and inflammatory cytokine and chemokine production in
monocytes and peripheral blood mononuclear cells. Furthermore, ZIKV infection in
trophoblasts induced lower IFN and higher inflammatory immune responses.
Placental inflammation is known to contribute to the risk of brain damage in
preterm newborns. Inhibition of toll-like receptor (TLR)3 and TLR8 each
abrogated the inflammatory cytokine responses in ZIKV-infected trophoblasts. Our
findings identify a potential link between maternal immune activation and
ZIKV-induced congenital diseases, and a potential therapeutic strategy that
targets TLR-mediated inflammatory responses in the placenta.