HPV11E7 inhibits IMQ-induced chemokine and colony-stimulating factor production in keratinocytes.

Abstract

Imiquimod (IMQ) is approved as a first-line treatment for genital warts caused by human papillomavirus (HPV) infection. However, the recurrence rate is very high. HPV E7 protein plays a critical role in HPV immune escape. However, the role of HPV11 E7 protein in genital warts recurrence during IMQ treatment is not clear. Here, we found that the expression profile of NHEK cells was obviously changed after IMQ treatment, and a large number of genes encoding cytokines and genes involved in cytokine-mediated signaling pathways and cellular metabolic signaling pathways were up- or downregulated. HPV11E7 overexpression inhibited the IMQ-induced production of of multiple chemokines and colony-stimulating factors in NHEK cells. Furthermore, we found that HPV11E7 could impair the activation of mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, our results suggested that HPV11 E7 diminishes the production of chemokines, colony-stimulating factors and other cytokines via inhibition of the MAPK signaling pathway, which suppresses the therapeutic effect of IMQ and promotes the recurrence of diseases, such as condyloma acuminatum.

• Authors: Huimin Zheng, Ziqi Zou, Xia Wu, Yaohan Xu, Jiang Zhu, Qiang Zhou, Rui Han, Yinjing Song, Hao Cheng
• Journal: Gene (Gene) Vol. 760 Pg. 145003 (Nov 15 2020) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 32739587 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Chemokines
• Colony-Stimulating Factors
• Cytokines
• E7 protein, human papillomavirus 11
• Oncogene Proteins, Viral
• Mitogen-Activated Protein Kinases
• Imiquimod

Topics

• Chemokines (biosynthesis, genetics, metabolism)
• Colony-Stimulating Factors (biosynthesis, metabolism)
• Cytokines (metabolism)
• Gene Expression (drug effects)
• Human papillomavirus 11 (metabolism)
• Humans
• Imiquimod (antagonists & inhibitors, pharmacology)
• Keratinocytes (drug effects, metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Oncogene Proteins, Viral (immunology, metabolism)
• Papillomavirus Infections (metabolism)
• Phosphorylation (drug effects)
• Signal Transduction (drug effects)