Scientists have used genetic engineering techniques to develop a new system that could aid identification of potential drug targets and treatments for human papillomavirus (HPV) infection, according to a PLOS Pathogens study.
HPVs include more than 200 subtypes and cause illnesses ranging from genital warts to throat and cervical cancer. Every year, six million people are diagnosed with new HPV infections in the U.S. alone. Doctors administer a wide variety of treatments for illnesses caused by HPVs, with varying success, but no specific cure for HPV infection yet exists.
To aid development of a cure, Mart Toots and colleagues of the Icosagen Cell Factory Ltd. and University of Tartu, Estonia have created a new method that enables identification of potentially effective drugs and drug targets. Unlike previously developed systems, their method takes into account the full HPV genome, as well as all three stages of the viral life cycle that occur during HPV infection.
To develop the new system, the researchers genetically engineered HPV genomes by adding "reporter genes" that code for bioluminescent proteins and allow for easy monitoring of viral growth at any life cycle stage. This enables the use of a method called high-throughput screening to quickly test the effects of many different chemicals on viral growth and identify potential drug candidates or drug targets.
The scientists demonstrated the new system by using it to screen more than 1000 chemical compounds in HPVs grown in cells derived from human tissue. They identified several compounds that blocked the growth of some HPV subtypes. Some of these compounds inhibit specific human cellular proteins that HPVs hijack to replicate inside the body, suggesting that these proteins could serve as targets in the development of new anti-HPV drugs.
"We are confident that the developed HPV drug screening assay system will allow to identify several different novel drug targets and small molecule drugs," the authors further explain. "These could be used effectively for elimination of cutaneous and mucosal low risk and high risk Human Papillomavirus infections, therefore addressing serious unmet medical need in society, like benign and malignant HPV positive epithelial tumours."
This work was supported by project EU42266 from the Enterprise Estonia (EAS) as well as by the IUT 20-27 from Estonian Research Council, research grants 9385 and 9467 from the Estonian Science Foundation and Center of Excellence in Chemical Biology (3.2.0101.08-0017). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Article: Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay, Toots M, Ustav M Jr, Männik A, Mumm K, Tämm K, Tamm T, et al., PLOS Pathogens, doi:10.1371/journal.ppat.1006168, published 9 February 2017.