To investigate whether antigenic SG proteins are capable of enhancing infection with Zika virus (ZIKV), a reemerging flavivirus primarily transmitted by the <i>Aedes aegypti</i> mosquito, we screened for antigenic SG proteins using a yeast display library and demonstrate that a previously undescribed SG protein we term neutrophil stimulating factor 1 (NeSt1) activates primary mouse neutrophils <i>ex vivo</i> Passive immunization against NeSt1 decreases pro-interleukin-1β and CXCL2 expression, prevents macrophages from infiltrating the bite site, protects susceptible IFNAR<sup>-/-</sup> IFNGR<sup>-/-</sup> (AG129) mice from early ZIKV replication, and ameliorates virus-induced pathogenesis.
The placental inflammatory response, specifically IL-1β secretion and signaling, is induced by ZIKV infection and represents an environmental factor that is known to increase the risk of perinatal developmental abnormalities.