A derivative of bovine herpesvirus 1 (BoHV-1) UL3.5 lacking the last forty amino acids inhibits replication of BoHV-1.

Bovine herpesvirus 1 (BoHV-1) UL3.5 is a tegument protein that interacts with BoHV-1 alpha-transinducing factor alphaBTIF). In this report, we show that a truncated UL3.5 lacking the last 40 amino acids (C40UL3.5) inhibited replication of BoHV-1. Stable expression of C40UL3.5 in MDBK cells inhibited replication of BoHV-1 300- to 500-fold in plaque assays. This inhibitory effect was specific for BoHV-1 as cells expressing C40UL3.5 supported replication of pseudorabies virus (species Suid herpesvirus 1, SuHV-1) and herpes simplex virus (species Human herpesvirus 1, HHV-1) to normal levels. In contrast, a truncated UL3.5 which lacked the first 20 amino acids and did not interact with alphaBTIF did not inhibit BoHV-1 replication. In the C40UL3.5-expressing cells infected with BoHV-1, expression of the viral immediate early gene BICP4 and the early protein gB were reduced and delayed. C40UL3.5, when either transiently or stably expressed, inhibited alphaBTIF-mediated transactivation of a BoHV-1 immediate-early promoter. C40UL3.5 may be useful for constructing transgenic cattle resistant to infection by BoHV-1.