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Background: It has been reported that programmed death-ligand 1 (PD-L1) is highly expressed in cells during viral infection, which helps the virus escape host immunity. However, the relationship between human papillomavirus (HPV) and PD-L1 in condyloma acuminatum and whether they participate in immunosuppression have not been reported. In this paper, we aimed to explore the expression and significance of PD-L1 in condyloma acuminatum., Methods: The expression of PD-L1 in the wart of condyloma acuminatum patients and the foreskin of healthy individuals was evaluated. Lentivirus transfection was used to introduce the HPV11-E7 gene into HaCaT cells to investigate whether HPV infection could affect the expression of PD-L1. The successfully constructed HPV11-E7 HaCaT cells were cocultured with Jurkat cells, and Jurkat cell apoptosis and proliferation as well as the Jurkat cell cycle were evaluated by flow cytometry and cell counting kit-8 (CCK-8) assays., Results: PD-L1 was highly expressed in keratinocytes of genital warts. Through the construction of a cell model, we found that HPV11-E7 could upregulate the expression of PD-L1 in HaCaT cells. Furthermore, HPV11-E7 HaCaT cells can promote the apoptosis of Jurkat cells, inhibit the proliferation of Jurkat cells and mediate the cell cycle arrest of Jurkat cells through the PD-1/PD-L1 signalling pathway., Conclusions: HPV infection may upregulate PD-L1 expression in the keratinocytes of genital warts and participate in the inhibition of local T-cell function., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Condylomata acuminata (CA) is caused by human papillomavirus (HPV) infections of keratinocytes and is a common sexually transmitted disease. The main clinical feature and risk of CA is the high recurrence of genital warts formed by infected keratinocytes. Metabolic reprogramming of most types of mammalian cells including keratinocytes can provide energy and intermediates essential for their survival. Here, we report that HPV infection develops a hypoxic microenvironment in CA warts by inducing the accumulation of glycogen and increased glycogen metabolism in the infected keratinocytes in a hypoxia-inducible factor 1α (HIF-1α) -dependent pathway. Our in vitro studies show that the increased glycogen metabolism is essential for the survival and proliferation of keratinocytes. Regarding its mechanism of action, glycogenolysis generates glucose-1-phosphate that fluxes into the pentose phosphate pathway and, then, generates abundant nicotinamide adenine dinucleotide phosphate, thereby ensuring high levels of glutathione in keratinocytes under hypoxia. The abrogation of glycogen synthesis and glycogenolysis decreases the ratio of glutathione and glutathione disulfide and increases the level of ROS, further resulting in the impairment of keratinocyte survival. Collectively, our work offers an insight into the metabolic reprogramming in the development of CA and implies that the intervention of glycogen metabolism would be a promising therapeutic target for CA., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)