Saydam Okay, Abril Carlos, Vogt Bernd, Ackermann Mathias, Schwyzer Martin
Faculty of Veterinary Medicine, Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland.
J Virol. 2004 Apr;78(8):3805-10. doi: 10.1128/jvi.78.8.3805-3810.2004.
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.
牛疱疹病毒1型（BHV-1）的即刻早期蛋白BICP0可反式激活多种病毒和细胞基因。在酵母双杂交cDNA文库筛选中，我们发现催化前列腺素D2（PGD2）生成的脂质运载蛋白型前列腺素D合成酶是BICP0的一个细胞靶点。我们观察到，在野生型BHV-1感染期间，细胞内PGD2水平升高，而培养基中的PGD2水平降低。在用表达β-半乳糖苷酶而非BICP0的重组BHV-1（A2G2）感染时，未观察到这些效应。瞬时表达试验表明，单独的BICP0会导致细胞中PGD2水平显著升高。PGD2可抑制培养细胞中BHV-1的复制。前列腺素的抗病毒活性早在很久以前就有文献记载，但其作用方式仍有待阐明。在此我们提供证据表明，PGD2会损害高效病毒复制所必需的BICP0的反式激活能力。
