Exploring the impact of small-molecule compounds on human papillomavirus type 5 replication and host cell differentiation
Date
2024
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Tartu Ülikool
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.
Description
Keywords
Human papillomavirus (HPV), HPV 5, Inhibition, Replication, Differentiation