Abstract
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.
Highlights
Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that infect the epithelium of the skin and mucosa
U2OS cells, which were obtained from the American Type Culture Collection (ATCC no: HTB-96), the modified cell lines U2OS GFP2-Firefly luciferase (Fluc) #10.15, U2OS-EBNA1 (Icosagen Cell Factory Ltd) and the HPV18 Rluc-E2-positive U2OS #10.15 subclones #2G10 and #2B3, were grown in Iscove’s modified Dulbecco’s medium (IMDM) supplemented with 10% fetal calf serum (FCS)
It is clear that addition of the Renilla luciferase coding sequence into the ORF of E2 protein did not alter the replication properties of HPV18 significantly compared to the wt genome
Summary
Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that infect the epithelium of the skin and mucosa. In addition to serious health problems, HPV-related infections and cancers are a serious economic burden: in the United States, a total of 3.4 billion is spent annually on the diagnosis and treatment of HPV-related cancers, which does not even account for the cost for treating various warts and other benign papillomas[10]. These numbers suggest that there is a clear need for better prevention and treatment solutions regarding HPV-related diseases
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