The Gale Lab has programs of study focused on trying to control virus infection during pregnancy and following transmission to the fetus. This program is particularly important in considerations of how to control progression of Zika virus infection and Oropouche virus infection as they emerge into population centers and endanger pregnant women.
We are applying systems biology approaches to identify control points of infection and innate immune activation that suppress virus replication and disease progression against these dangerous viruses.
Diagram of ZIKV inhibition of Akt signaling in trophoblast cells.
Zika virus (ZIKV) infection in trophoblast cells leads to the inhibition of HSP90, primarily mediated by the NS5 protein, which interferes with the proper stabilization of Akt and other HSP90-dependent kinases. This inhibition prevents Akt from being activated by maternal growth factors such as EGF. Consequently, Akt signaling is disrupted, contributing to its degradation. A decrease in p-Akt levels leads to reduced cytoskeletal rearrangement, glucose uptake, protein synthesis, and proliferation, all of which are essential for effective trophoblast migration. The impaired Akt pathway hampers trophoblast migration into the maternal decidua. This results in the formation of immature placental villi incapable of supporting a developing fetus. These effects can contribute to placental immaturity, potentially leading to fetal growth restriction or, in severe cases, fetal demise. Hajari et al., 2026.