王馨艺;路一平;孙峥嵘;

• 1:中国医科大学附属盛京医院生物样本库

摘要(Abstract)：

人乳头瘤病毒（Human papillomavirus,HPV）为双链环状小DNA病毒，它不仅能引起黏膜上皮的良性增生，也可以导致癌症如宫颈癌、阴茎癌、口咽癌的发生。HPV重组细胞模型的建立及其分化培养，可以应用于HPV早期感染、HPV感染对宿主细胞生命周期影响的研究，也可进一步诱导，用于深入研究DNA损伤修复途径对病毒复制的影响、以及HPV整合机制。本文将主要围绕HPV重组细胞模型的建立、分化培养的方法以及重组细胞模型的应用进行综述。

关键词(KeyWords)： 人乳头瘤病毒;HPV重组细胞模型;分化培养

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金（项目号：82000076）,题目：TREM2调节脂肪酸氧化促进肺泡巨噬细胞极化在特发性肺纤维化中的作用机制研究~~

作者(Authors): 王馨艺;路一平;孙峥嵘;

DOI: 10.13242/j.cnki.bingduxuebao.004251

参考文献(References)：

• [1] Human papillomavirus vaccines:WHO position paper,May 2017-Recommendations[J/OL]. Vaccine, 2017,35(43):5753-5755. DOI:10.1016/j.vaccine.2017.05.069.
• [2] Doorbar J, Quint W, Banks L, Bravo I G, Stoler M,Broker T R, Stanley M A. The biology and life-cycle of human papillomaviruses[J/OL]. Vaccine, 2012, 30Suppl 5:F55-70. DOI:10.1016/j.vaccine.2012.06.083.
• [3] Bernard H U, Burk R D, Chen Z, van Doorslaer K, zur Hausen H, de Villiers E M. Classification of papillomaviruses(PVs)based on 189 PV types and proposal of taxonomic amendments[J/OL]. Virology,2010, 401(1):70-79. DOI:10.1016/j.virol.2010.02.002.
• [4] Bhatla N, Singhal S. Primary HPV screening for cervical cancer[J/OL]. Best Pract Res Clin Obstet Gynaecol, 2020, 65:98-108. DOI:10.1016/j.bpobgyn.2020.02.008.
• [5]王莹莹，李传印，姚宇峰. HPV16型基因变异与宫颈癌发生相关性的研究进展[J/OL].病毒学报，2021, 37(05):1197-1207. DOI:10.13242/j. cnki.bingduxuebao.003964.
• [6] Wang R, Pan W, Jin L, Huang W, Li Y, Wu D, Gao C, Ma D, Liao S. Human papillomavirus vaccine against cervical cancer:Opportunity and challenge[J/OL]. Cancer Lett, 2020, 471:88-102.DOI:10.1016/j.canlet.2019.11.039.
• [7] Giuliano A R, Nyitray A G, Kreimer A R, Pierce Campbell C M, Goodman M T, Sudenga S L,Monsonego J, Franceschi S. EUROGIN 2014roadmap:differences in human papillomavirus infection natural history, transmission and human papillomavirusrelated cancer incidence by gender and anatomic site of infection[J/OL]. Int J Cancer, 2015, 136(12):2752-2760.DOI:10.1002/ijc.29082.
• [8]刘淼，吴盈盈，路一平，吴思，王爽，崔畅婉，于淼，孙峥嵘.中国东北地区人乳头瘤病毒16型全基因组克隆及HPV16.HaCaT重组细胞模型的构建及初步鉴定[J/OL].病毒学报，2021, 37(05):1051-1059. DOI:10.13242/j.cnki.bingduxuebao.004029.
• [9] Kaminski P, Hong S, Kono T, Hoover P, Laimins L.Topoisomerase 2β induces DNA breaks to regulate human papillomavirus replication[J/OL]. mBio, 2021,12(1).DOI:10.1128/mBio.00005-21.
• [10]Wilson V G. Growth and differentiation of HaCaT keratinocytes[J/OL]. Methods Mol Biol, 2014, 1195:33-41.DOI:10.1007/7651_2013_42.
• [11]Lehr E E, Qadadri B, Brown C R, Brown D R. Human papillomavirus type 59 immortalized keratinocytes express late viral proteins and infectious virus after calcium stimulation[J/OL]. Virology, 2003, 314(2):562-571.DOI:10.1016/s0042-6822(03)00492-6.
• [12]Roman B R, Aragones A. Epidemiology and incidence of HPV-related cancers of the head and neck[J/OL]. J Surg Oncol, 2021, 124(6):920-922. DOI:10.1002/jso.26687.
• [13]Spriggs C C, Blanco L Z, Maniar K P, Laimins L A.Expression of HPV-induced DNA damage repair factors correlates with cin progression[J/OL]. Int J Gynecol Pathol, 2019, 38(1):1-10. DOI:10.1097/PGP.0000000000000477.
• [14]Zhang J, Yang P, Liu D, Gao M, Wang J, Wang X,Liu Y, Zhang X. c-Myc Upregulated by High Glucose Inhibits HaCaT Differentiation by S100A6transcriptional activation[J/OL]. Front Endocrinol(Lausanne), 2021, 12:676403. DOI:10.3389/fendo.2021.676403.
• [15]Cheng S, Schmidt-Grimminger D C, Murant T, Broker T R, Chow L T. Differentiation-dependent upregulation of the human papillomavirus E7 gene reactivates cellular DNA replication in suprabasal differentiated keratinocytes[J/OL]. Genes Dev, 1995, 9(19):2335-2349.DOI:10.1101/gad.9.19.2335.
• [16]Lambert P F, Ozbun M A, Collins A, Holmgren S,Lee D, Nakahara T. Using an immortalized cell line to study the HPV life cycle in organotypic"raft"cultures[J/OL]. Methods Mol Med, 2005, 119:141-155. DOI:10.1385/1-59259-982-6:141.
• [17]Flores E R, Allen-Hoffmann B L, Lee D, Lambert P F. The human papillomavirus type 16 E7 oncogene is required for the productive stage of the viral life cycle[J/OL]. J Virol, 2000, 74(14):6622-6631. DOI:10.1128/jvi.74.14.6622-6631.2000.
• [18]Genther S M, Sterling S, Duensing S, Münger K,Sattler C, Lambert P F. Quantitative role of the human papillomavirus type 16 E5 gene during the productive stage of the viral life cycle[J/OL]. J Virol, 2003, 77(5):2832-2842. DOI:10.1128/jvi. 77.5.2832-2842.2003.
• [19]Brown D R, Bryan J T, Pratt L, Handy V, Fife K H,Stoler M H. Human papillomavirus type 11 E1--E4 and L1 proteins colocalize in the mouse xenograft system at multiple time points[J/OL]. Virology, 1995, 214(1):259-263. DOI:10.1006/viro.1995.9931.
• [20]Wang Y, Li X, Song S, Wu J. Development of BasalLike HaCaT Keratinocytes Containing the Genome of Human Papillomavirus(HPV)Type 11 for Screening of Anti-HPV Effects[J/OL]. J Biomol Screen, 2014, 19(8):1154-1163.DOI:10.1177/1087057114536987.
• [21]Kaczkowski B, Rossing M, Andersen D K, Dreher A,Morevati M, Visser M A, Winther O, Nielsen F C,Norrild B. Integrative analyses reveal novel strategies in HPV11,-16 and-45 early infection[J/OL]. Sci Rep,2012, 2:515.DOI:10.1038/srep00515.
• [22]Ozbun M A. Human papillomavirus type 31b infection of human keratinocytes and the onset of early transcription[J/OL]. J Virol, 2002, 76(22):11291-11300. DOI:10.1128/jvi.76.22.11291-11300.2002.
• [23]Pett M R, Herdman M T, Palmer R D, Yeo G S,Shivji M K, Stanley M A, Coleman N. Selection of cervical keratinocytes containing integrated HPV16associates with episome loss and an endogenous antiviral response[J/OL]. Proc Natl Acad Sci U S A, 2006, 103(10):3822-3827.DOI:10.1073/pnas.0600078103.
• [24]Peitsaro P, Hietanen S, Johansson B, Lakkala T,Syrj?nen S. Single copy heterozygote integration of HPV33 in chromosomal band 5p14 is found in an epithelial cell clone with selective growth advantage[J/OL].Carcinogenesis, 2002, 23(6):1057-1064. DOI:10.1093/carcin/23.6.1057.
• [25]Spartz H, Lehr E, Zhang B, Roman A, Brown D R.Progression from productive infection to integration and oncogenic transformation in human papillomavirus type59-immortalized foreskin keratinocytes[J/OL].Virology, 2005, 336(1):11-25. DOI:10.1016/j.virol.2005.02.026.
• [26]Hong S, Li Y, Kaminski P J, Andrade J, Laimins L A.Pathogenesis of human papillomaviruses requires the atr/p62 autophagy-related pathway[J/OL]. mBio, 2020, 11(4).DOI:10.1128/mBio.01628-20.
• [27]孙洋.HPV11.HaCaT重组细胞作为体外药效学模型的完整性和应用性研究[D].北京：北京协和医学院，2016.
• [28]Hebner C M, Laimins L A. Human papillomaviruses:basic mechanisms of pathogenesis and oncogenicity[J/OL]. Rev Med Virol, 2006, 16(2):83-97. DOI:10.1002/rmv.488.
• [29]Doorbar J. The papillomavirus life cycle[J/OL]. J Clin Virol, 2005, 32 Suppl 1:S7-15. DOI:10.1016/j.jcv.2004.12.006.
• [30]Harden M E, Munger K. Human papillomavirus molecular biology[J/OL]. Mutat Res Rev Mutat Res,2017, 772:3-12.DOI:10.1016/j.mrrev.2016.07.002.
• [31]Hong S Y. DNA damage response is hijacked by human papillomaviruses to complete their life cycle[J/OL]. J Zhejiang Univ Sci B, 2017, 18(3):215-232. DOI:10.1631/jzus.B1600306.
• [32]Green H. Terminal differentiation of cultured human epidermal cells[J/OL]. Cell, 1977, 11(2):405-416.DOI:10.1016/0092-8674(77)90058-7.
• [33]Ruesch M N, Stubenrauch F, Laimins L A. Activation of papillomavirus late gene transcription and genome amplification upon differentiation in semisolid medium is coincident with expression of involucrin and transglutaminase but not keratin-10[J/OL]. J Virol,1998, 72(6):5016-5024.DOI:10.1128/JVI.72.6.5016-5024.1998.
• [34]Hong S, Cheng S, Iovane A, Laimins L A. STAT-5regulates transcription of the topoisomerase IIβ-Binding Protein 1(TopBP1)gene to activate the atr pathway and promote human papillomavirus replication[J/OL].mBio, 2015, 6(6):e02006-02015. DOI:10.1128/mBio.02006-15.
• [35]Deyrieux A F, Wilson V G. In vitro culture conditions to study keratinocyte differentiation using the HaCaT cell line[J/OL]. Cytotechnology, 2007, 54(2):77-83.DOI:10.1007/s10616-007-9076-1.
• [36]Wilson R, Ryan G B, Knight G L, Laimins L A,Roberts S. The full-length E1E4 protein of human papillomavirus type 18 modulates differentiationdependent viral DNA amplification and late gene expression[J/OL]. Virology, 2007, 362(2):453-460.DOI:10.1016/j.virol.2007.01.005.
• [37]Lee C, Wooldridge T R, Laimins L A. Analysis of the roles of E6 binding to E6TP1 and nuclear localization in the human papillomavirus type 31 life cycle[J/OL].Virology, 2007, 358(1):201-210. DOI:10.1016/j.virol.2006.08.028.
• [38]Moody C A, Laimins L A. Human papillomaviruses activate the ATM DNA damage pathway for viral genome amplification upon differentiation[J/OL]. PLoS Pathog, 2009, 5(10):e1000605.DOI:10.1371/journal.ppat.1000605
• [39]Albert E, Laimins L. Regulation of the human papillomavirus life cycle by dna damage repair pathways and epigenetic factors[J/OL]. Viruses, 2020, 12(7).DOI:10.3390/v12070744.
• [40]Hong S, Xu J, Li Y, Andrade J, Hoover P, Kaminski P J, Laimins L A. Topoisomerase IIβ-binding protein 1activates expression of E2F1 and p73 in HPV-positive cells for genome amplification upon epithelial differentiation[J/OL]. Oncogene, 2019, 38(17):3274-3287.DOI:10.1038/s41388-018-0633-1.
• [41]Della Fera A N, Warburton A, Coursey T L, Khurana S, McBride A A. Persistent human papillomavirus infection[J/OL]. Viruses, 2021, 13(2).DOI:10.3390/v13020321.
• [42]McBride A A. Mechanisms and strategies of papillomavirus replication[J/OL]. Biol Chem, 2017,398(8):919-927.DOI:10.1515/hsz-2017-0113.
• [43]McBride A A, Warburton A. The role of integration in oncogenic progression of HPV-associated cancers[J/OL]. PLoS Pathog, 2017, 13(4):e1006211. DOI:10.1371/journal.ppat.1006211.
• [44]黄莎莎，郝登再，张岩，刘厚明，单万水.高危型HPV DNA整合导致宫颈癌的作用机制和临床检测进展[J/OL].遗传，2017,39(09):775-783. DOI:10.16288/j.yczz.17-151.
• [45]Integrated genomic and molecular characterization of cervical cancer[J/OL]. Nature, 2017, 543(7645):378-384.DOI:10.1038/nature21386.
• [46]Bodelon C, Untereiner M E, Machiela M J,Vinokurova S, Wentzensen N. Genomic characterization of viral integration sites in HPV-related cancers[J/OL].Int J Cancer, 2016, 139(9):2001-2011.DOI:10.1002/ijc.30243.