Suppressors of Cytokine Signaling and Protein Inhibitors of Activated Signal Transducer and Activator of Transcriptions As Therapeutic Targets in Flavivirus Infections

Flaviviruses cause significant human diseases putting more than 400 million people at risk annually worldwide. Because of migration and improved transportation, these viruses can be found on all continents (except Antarctica). Although a majority of the viruses are endemic in the tropics, a few [West Nile virus (WNV) and tick-borne encephalitis virus (TBEV)] have shown endemicity in Europe and North America. Currently, there are vaccines for the Yellow fever virus, Japanese encephalitis virus, and TBEV, but there is no effective vaccine and/or therapy against all other flaviviruses. Although there are intensive efforts to develop vaccines for Zika viruses, dengue viruses, and WNVs, there is the need for alternative or parallel antiviral therapeutic approaches. Suppressors of cytokine signaling (SOCS) and protein inhibitors of activated signal transducer and activator of transcription (STATs; PIAS), both regulatory proteins of the Janus kinase/STAT signaling pathway, have been explored as therapeutic targets in herpes simplex and vaccinia viruses, as well as in cancer therapy. In this review, we briefly describe the function of SOCS and PIAS and their therapeutic potential in flaviviral infections. [Figure: see text].