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 D(2) (PGD(2)), is a cellular target of BICP0. We observed that, during wild-type BHV-1 infection, PGD(2) levels were increased intracellularly and decreased in the medium. These effects were absent upon infection with recombinant BHV-1 expressing beta-galactosidase instead of BICP0 (A2G2). Transient-expression assays showed that BICP0 alone caused a significant increase in PGD(2) levels in the cell. PGD(2) 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 PGD(2) impairs the transactivation ability of BICP0 that is necessary for efficient virus replication.
Saydam
Okay
O
Faculty of Veterinary Medicine, Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland.
Abril
Carlos
C
Vogt
Bernd
B
Ackermann
Mathias
M
Schwyzer
Martin
M
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D006367:HeLa Cells; D007242:Herpesvirus 1, Bovine / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D054834:Lipocalins; D015230:Prostaglandin D2 / Q000378:metabolism* / Q000494:pharmacology; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D004279:DNA, Viral; D054834:Lipocalins; D015534:Trans-Activators; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; C086729:bICP0 protein, Bovine herpesvirus 1; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2