eIF4A3 inhibits pseudorabies virus replication by facilitating antiviral immune response.

Abstract

Eukaryotic translation initiation factor 4A3 (eIF4A3)-mediated RNA metabolism is essential for cellular homeostasis and viral replication. However, its role in regulating antiviral innate immunity during pseudorabies virus (PRV) infection remains unknown. Here, we demonstrate that eIF4A3 protein expression was significantly downregulated both in vitro and in vivo during PRV infection. Functional assays showed that eIF4A3 overexpression suppressed PRV replication, whereas its knockdown enhanced viral replication. Mechanistically, eIF4A3 inhibited mA modification of STING mRNA, thereby increasing its stability. Elevated STING protein expression promoted type I interferon (IFN-β) production via activation of the cGAS-STING signaling pathway. In summary, this study identifies a new antiviral mechanism in which eIF4A3 enhances innate immunity against PRV infection by regulating the stability of STING mRNA through modulating its m⁶A modification.