人乳头瘤病毒16型感染上皮细胞过程的研究进展  

Research Progress on the Infection Procedure of Human Papillomavirus Type 16 to Epithelial Cells

作　　者：曹琳 池鑫 韩峰[2] 俞海[1] 李少伟[1,2] CAO Lin;CHI Xin;HAN Feng;YU Hai;LI Shaowei(School of Public Health,State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics,Xiamen University,Xiamen 361102,China;School of Life Science,National Institute of Diagnostics and Vaccine Development of Infectious Diseases,Xiamen University,Xiamen 361101,China)

机构地区：[1]厦门大学分子疫苗学与分子诊断学国家重点实验室公共卫生学院,厦门361102 [2]厦门大学国家传染病诊断试剂与疫苗工程技术研究中心生命科学学院,厦门361102

出　　处：《病毒学报》2025年第1期232-244,共13页Chinese Journal of Virology

基　　金：国家自然科学基金(项目号82271873),题目:以T=7人乳头瘤类病毒颗粒为基座可化学缀合多种对称性寡聚抗原的通用纳米颗粒疫苗分子;厦门市自然科学基金(项目号3502Z20227165),题目:基于组学的大肠杆菌可溶性外源表达的调控机制研究。

摘　　要：宫颈癌是全球第四大常见的女性恶性肿瘤,人乳头瘤病毒(Human papillomavirus,HPV)是已知导致宫颈癌的主要病原体,特别是高危型HPV16和HPV18。HPV入胞及胞内转运过程尚存在争论。近期,研究人员发现除了经典的逆转复合体(Retromer),寻回复合体(Retriever)也参与HPV的胞内转运。本文主要综述了近十年HPV16进入宿主细胞的早期过程,概述了病毒粒子如何从细胞外基质通过黏膜上皮进入宿主细胞,并描述了内化后所经历的一系列复杂信号转导和胞内转运过程。HPV16病毒粒子首先与硫酸乙酰肝素蛋白聚糖(Heparan sulfate proteoglycan,HSPG)结合,经历构象变化形成入胞复合物进入内体,经逆转复合体和寻回复合体转运至高尔基体并在有丝分裂期G2/M期入核。深入理解该病毒的宿主侵染机制及其产生的免疫反应对设计针对HPV感染相关及其导致的宫颈癌等的治疗策略具有重要的意义,本综述将为HPV治疗性疫苗设计和宫颈癌的抗病毒药物开发提供基础的病毒学信息。Cervical cancer ranks as the fourth most prevalent malignancy among women globally,primarily attributed to infection by human papillomavirus(HPV),notably high-risk strains HPV16 and HPV18.The mechanisms governing HPV virion entry and subsequent intracellular trafficking remain a subject of ongoing research.Recent studies have identified that alongside the well-known retromer complex,the retriever complex is also implicated in the intracellular transport of HPV.This review systematically summarized the initial steps of HPV16 cell entry reported over the last decade,detailing the entry of virus particles from the extracellular matrix into host cells via the mucosal epithelium and elaborating the complex signal transduction and intracellular transport mechanisms that follow internalization.Initially,HPV16 virions bind to heparin sulfate proteoglycans(HSPG),undergo structural modifications to form endocytosis complexes for endosome entry.The complexes are subsequently transported to the Golgi apparatus by both retromer and retriever complexes,and ultimately entering the nucleus in the mitotic G2/M phase.An in-depth understanding of HPV's invasion strategies and induced immune responses is crucial for developing effective treatments against HPV infections and resultant cervical cancer.This review aims to provide essential virological insights for developing therapeutic HPV vaccines and advancing antiviral therapies for cervical cancer.

关 键 词：人乳头瘤病毒 HPV16 胞内转运 逆行运输 

分 类 号：R373.9[医药卫生—病原生物学]