Exploring the impact of small-molecule compounds on human papillomavirus type 5 replication and host cell differentiation

Abstract

Human papillomavirus (HPV) is the most widely spread sexually transmitted virus worldwide. Different types of HPVs can cause skin lesions and cancers. HPV5 belongs to beta papillomavirus and is commonly found in healthy skin, while also associated with skin cancer in patients with immune deficiency or a genetic disorder, Epidermodysplasia verruciformis. Vaccines preventing infection with the most carcinogenic mucosal HPV types exist, but they are inefficient against cutaneous HPVs. Also, there is no effective treatment for existing infections, which emphasizes the need to develop antiviral drugs. The present thesis focuses on two small-molecule compounds (#1 and #2) identified through a high-throughput screening performed prior to this study. The aim was to confirm their inhibitory effect on HPV5 replication and to determine the effect of the identified inhibitors on the differentiation of human osteosarcoma (U2OS) cells and human primary epithelial keratinocytes (HPEKs), which are used as HPV model host cells. Both compounds showed a strong inhibitory effect on the HPV5 replication in U2OS cells, and the inhibitory activity of the compound #2 was confirmed also in HPEKs. However, in contrast to the compound #2, the compound #1 upregulated the HPV5 replication in HPEKs, which was explained by the differentiation-inducing effect. Thus, the compound #2 was chosen as a potential HPV5 replication inhibitor for future investigation.