ISG expression screening reveals the family-specific antibunyaviral activity of ISG20

Order Bunyavirales poses a significant threat to the agricultural industry, animal husbandry and human welfare. In response to viral infections, interferons (IFNs) trigger the expression of numerous interferon stimulated genes (ISGs) whose concerted action can potently inhibit the replication of bunyaviruses. We used a FACS-based method to screen the ability of ~500 unique ISGs from humans or rhesus macaques to inhibit the replication of Bunyamwera virus (BUNV), the prototype of both the Peribunyaviridae family and Bunyavirales order. Candidates possessing antibunyaviral activity were further examined using a panel of divergent bunyaviruses in family Peribunyaviridae, Hantaviridae, Nairoviridae and Phenuiviridae.