Transactivator Protein BICP0 of Bovine Herpesvirus 1 (BHV-1) Is Blocked by Prostaglandin D₂ (PGD₂), Which Points to a Mechanism for PGD₂-Mediated Inhibition of BHV-1 Replication

The immediate-early protein, BICP0, of bovine herpesvirus 1 (BHV-1) transactivates a variety of viral and cellular genes. In a yeast two-hybrid cDNA library screening, we found that lipocalin-type prostaglandin D synthase, which catalyzes the production of prostaglandin D₂ (PGD₂), is a cellular target of BICP0. We observed that, during wild-type BHV-1 infection, PGD₂ levels were increased intracellularly and decreased in the medium. These effects were absent upon infection with recombinant BHV-1 expressing β-galactosidase instead of BICP0 (A2G2). Transient-expression assays showed that BICP0 alone caused a significant increase in PGD₂ levels in the cell. PGD₂ repressed BHV-1 replication in cultured cells. Antiviral activities of prostaglandins have been documented long ago, but their mode of action remains to be clarified. Here we provide evidence that PGD₂ impairs the transactivation ability of BICP0 that is necessary for efficient virus replication.