Sandler A B, Vande Pol S B, Spalholz B A
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
J Virol. 1993 Sep;67(9):5079-87. doi: 10.1128/JVI.67.9.5079-5087.1993.
Bovine papillomavirus type 1 (BPV-1) is the prototype virus for the study of papillomavirus gene regulation. The functions of the BPV-1 E2 proteins in transcriptional regulation have been well characterized. The BPV-1 E1 protein is required for viral DNA replication and can bind to the origin of replication alone or in a complex with the E2 transactivator protein. In this study, we demonstrated that the BPV-1 E1 protein is also involved in transcriptional regulation. The E1 protein significantly repressed E2-transactivated transcription from the major early promoter P89. This activity is consistent with the elevated level of P89 transcription observed in BPV-1 E1 open reading frame mutants. Transcriptional repression by E1 correlated with the ability of an E1-E2 protein complex to bind the replication origin but was not dependent on viral DNA replication. These studies identify a new mechanism involved in the regulation of papillomavirus transcription which has implications regarding expression of the viral transforming functions.
牛乳头瘤病毒1型(BPV-1)是用于研究乳头瘤病毒基因调控的原型病毒。BPV-1 E2蛋白在转录调控中的功能已得到充分表征。BPV-1 E1蛋白是病毒DNA复制所必需的,它可以单独与复制起点结合,也可以与E2反式激活蛋白形成复合物后结合。在本研究中,我们证明BPV-1 E1蛋白也参与转录调控。E1蛋白显著抑制了主要早期启动子P89的E2反式激活转录。这种活性与在BPV-1 E1开放阅读框突变体中观察到的P89转录水平升高一致。E1介导的转录抑制与E1-E2蛋白复合物结合复制起点的能力相关,但不依赖于病毒DNA复制。这些研究确定了一种参与乳头瘤病毒转录调控的新机制,这对病毒转化功能的表达具有重要意义。