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.

咪喹莫特（IMQ）被批准作为由人乳头瘤病毒（HPV）感染引起的生殖器疣的一线治疗药物。但是，复发率很高。HPV E7蛋白在HPV免疫逃逸中起关键作用。然而，在IMQ治疗期间HPV11 E7蛋白在生殖器疣复发中的作用尚不清楚。在这里，我们发现在IMQ处理后，NHEK细胞的表达谱发生了明显变化，并且大量编码细胞因子的基因以及与细胞因子介导的信号通路和细胞代谢信号通路有关的基因被上调或下调。HPV11E7的过表达抑制了NHEK细胞中IMQ诱导的多种趋化因子和集落刺激因子的产生。此外，我们发现HPV11E7可能会破坏丝裂原活化蛋白激酶（MAPK）信号通路的激活。