Tummers Bart, Burg Sjoerd H Van Der
Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Viruses. 2015 May 21;7(5):2485-506. doi: 10.3390/v7052485.
Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review.
高危型人乳头瘤病毒（hrHPV）持续感染可发展为癌症。高危型HPV感染角质形成细胞（KC），尽管KC具备检测并启动针对入侵病原体的免疫反应的能力，但高危型HPV仍能成功抑制宿主免疫长达两年。病毒持续性感染是通过主动干扰KC的固有免疫和适应性免疫机制来实现的。为此，高危型HPV利用其病毒基因组编码的蛋白质，以及利用细胞蛋白质来干扰固有免疫和适应性免疫途径的信号传导。这导致干扰素和促炎细胞因子产生受损以及随后的免疫细胞吸引，同时对免疫系统传入信号产生抗性。此外，高危型HPV通过干扰抗原呈递给抗原特异性细胞毒性T淋巴细胞来避免感染细胞被杀伤。因此，高危型HPV已进化出多种机制来逃避固有免疫系统和适应性免疫系统的检测与清除，本综述将详细阐述其分子机制。
