Bovine herpesvirus 1 tegument protein UL41 suppresses antiviral innate immune response via directly targeting STAT1.

Bovine herpesvirus 1 (BoHV-1) has the ability to escape the host innate immune response and establish a long-term latent infection. The tegument protein UL41 causes the rapid degradation of existing and newly transcribed host mRNA and promote the expression of viral protein in the early stages of a productive infection. At present, how BoHV-1 UL41 evades JAK-STAT signaling pathway is unclear. In this study, we report that UL41 expression facilitates BoHV-1 replication and represses the generation of ISGs. Constitutive expression of UL41 inhibits the expression of STAT1, and treatment with drugs that inhibit the protein-degrading pathway did not restore STAT1 expression. Further study shows that UL41 binds and cleaves the mRNA of STAT1, thus blocks the formation of IFN-stimulated gene factor 3 complexes, and represses the activity of IFN response elements and the generation of ISGs. In brief, our results reveal a novel mechanism of BoHV-1 UL41 against natural innate immunity through direct targeting of the STAT1 transcript.