Toots Mart, Ustav Mart, Männik Andres, Mumm Karl, Tämm Kaido, Tamm Tarmo, Ustav Ene, Ustav Mart
Institute of Technology, University of Tartu, Tartu, Estonia.
Icosagen Cell Factory OÜ, Ülenurme vald, Tartumaa, Estonia.
PLoS Pathog. 2017 Feb 9;13(2):e1006168. doi: 10.1371/journal.ppat.1006168. eCollection 2017 Feb.
Human papillomaviruses (HPVs) are oncogenic viruses that cause numerous different cancers as well as benign lesions in the epithelia. To date, there is no effective cure for an ongoing HPV infection. Here, we describe the generation process of a platform for the development of anti-HPV drugs. This system consists of engineered full-length HPV genomes that express reporter genes for evaluation of the viral copy number in all three HPV replication stages. We demonstrate the usefulness of this system by conducting high-throughput screens to identify novel high-risk HPV-specific inhibitors. At least five of the inhibitors block the function of Tdp1 and PARP1, which have been identified as essential cellular proteins for HPV replication and promising candidates for the development of antivirals against HPV and possibly against HPV-related cancers.
人乳头瘤病毒（HPV）是致癌病毒，可导致多种不同癌症以及上皮组织中的良性病变。迄今为止，对于持续的HPV感染尚无有效的治疗方法。在此，我们描述了一个用于开发抗HPV药物的平台的生成过程。该系统由工程化的全长HPV基因组组成，这些基因组表达报告基因，用于评估所有三个HPV复制阶段的病毒拷贝数。我们通过进行高通量筛选以鉴定新型高危HPV特异性抑制剂，证明了该系统的实用性。至少有五种抑制剂可阻断Tdp1和PARP1的功能，这两种蛋白已被确定为HPV复制所必需的细胞蛋白，也是开发针对HPV以及可能针对HPV相关癌症的抗病毒药物的有前景的候选靶点。
