Abstract
Human papillomavirus (HPV) is associated with infection of different tissues, such as the cervix, anus, vagina, penis, vulva, oropharynx, throat, tonsils, back of the tongue, skin, the lungs, among other tissues. HPV infection may or may not be associated with the development of cancer, where HPVs not related to cancer are defined as low-risk HPVs and are associated with papillomatosis disease. In contrast, high-risk HPVs (HR-HPVs) are associated with developing cancers in areas that HR-HPV infects, such as the cervix. In general, infection of HPV target cells is regulated by specific molecules and receptors that induce various conformational changes of HPV capsid proteins, allowing activation of HPV endocytosis mechanisms and the arrival of the HPV genome to the human cell nucleus. After the transcription of the HPV genome, the HPV genome duplicates exponentially to lodge in a new HPV capsid, inducing the process of exocytosis of HPV virions and thus releasing a new HPV viral particle with a high potential of infection. This infection process allows the HPV viral life cycle to conclude and enables the growth of HPV virions. Understanding the entire infection process has been a topic that researchers have studied and developed for decades; however, there are many things to still understand about HPV infection. A thorough understanding of these HPV infection processes will allow new potential treatments for HPV-associated cancer and papillomatosis. This chapter focuses on HPV infection, the process that will enable HPV to complete its HPV life cycle, emphasizing the critical role of different molecules in allowing this infection and its completion during the HPV viral life cycle.
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References
Abban CY, Meneses PI (2010) Usage of heparan sulfate, integrins, and FAK in HPV16 infection. Virology 403:1–16. https://doi.org/10.1016/j.virol.2010.04.007
Aydin I, Villalonga-Planells R, Greune L et al (2017) A central region in the minor capsid protein of papillomaviruses facilitates viral genome tethering and membrane penetration for mitotic nuclear entry. PLoS Pathog 13:e1006308. https://doi.org/10.1371/journal.ppat.1006308
Bergant Marušič M, Ozbun MA, Campos SK et al (2012) Human papillomavirus L2 facilitates viral escape from late endosomes via sorting nexin 17. Traffic 13:455–467. https://doi.org/10.1111/j.1600-0854.2011.01320.x
Bergvall M, Melendy T, Archambault J (2013) The E1 proteins. Virology 445:35–56. https://doi.org/10.1016/j.virol.2013.07.020
Bernard H-U (2013) Regulatory elements in the viral genome. Virology 445:197–204. https://doi.org/10.1016/j.virol.2013.04.035
Bonnez W, DaRin C, Borkhuis C et al (1998) Isolation and propagation of human papillomavirus type 16 in human xenografts implanted in the severe combined immunodeficiency mouse. J Virol 72:5256–5261. https://doi.org/10.1128/JVI.72.6.5256-5261.1998
Bousarghin L, Touzé A, Sizaret P-Y, Coursaget P (2003) Human papillomavirus types 16, 31, and 58 use different endocytosis pathways to enter cells. J Virol 77:3846–3850. https://doi.org/10.1128/jvi.77.6.3846-3850.2003
Boyer SN, Wazer DE, Band V (1996) E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway. Cancer Res 56:4620–4624
Buck CB, Thompson CD, Pang Y-YS et al (2005) Maturation of papillomavirus capsids. J Virol 79:2839–2846. https://doi.org/10.1128/JVI.79.5.2839-2846.2005
Clark MA, Hartley A, Geh JI (2004) Cancer of the anal canal. Lancet Oncol 5:149–157. https://doi.org/10.1016/S1470-2045(04)01410-X
Crusius K, Auvinen E, Steuer B et al (1998) The human papillomavirus type 16 E5-protein modulates ligand-dependent activation of the EGF receptor family in the human epithelial cell line HaCaT. Exp Cell Res 241:76–83. https://doi.org/10.1006/excr.1998.4024
Cruz-Gregorio A, Manzo-Merino J, Gonzaléz-García MC et al (2018a) Human papillomavirus types 16 and 18 early-expressed proteins differentially modulate the cellular redox state and DNA damage. Int J Biol Sci 14:21–35. https://doi.org/10.7150/ijbs.21547
Cruz-Gregorio A, Manzo-Merino J, Lizano M (2018b) Cellular redox, cancer and human papillomavirus. Virus Res 246:35–45. https://doi.org/10.1016/j.virusres.2018.01.003
Cruz-Gregorio A, Aranda-Rivera AK, Aparicio-Trejo OE et al (2019) E6 Oncoproteins from high-risk human papillomavirus induce mitochondrial metabolism in a head and neck squamous cell carcinoma model. Biomol Ther 9:351. https://doi.org/10.3390/biom9080351
Cruz-Gregorio A, Aranda-Rivera AK, Pedraza-Chaverri J (2020) Human papillomavirus-related cancers and mitochondria. Virus Res 286:198016. https://doi.org/10.1016/j.virusres.2020.198016
Cruz-Gregorio A, Aranda-Rivera AK, Pedraza-Chaverri J (2022) Pathological similarities in the development of papillomavirus-associated cancer in humans, dogs, and cats. Animals (Basel) 12:2390. https://doi.org/10.3390/ani12182390
Cruz-Gregorio A, Aranda-Rivera AK, Roviello GN, Pedraza-Chaverri J (2023) Targeting mitochondrial therapy in the regulation of HPV infection and HPV-related cancers. Pathogens 12:402. https://doi.org/10.3390/pathogens12030402
Culp TD, Budgeon LR, Christensen ND (2006a) Human papillomaviruses bind a basal extracellular matrix component secreted by keratinocytes which is distinct from a membrane-associated receptor. Virology 347:147–159. https://doi.org/10.1016/j.virol.2005.11.025
Culp TD, Budgeon LR, Marinkovich MP et al (2006b) Keratinocyte-secreted laminin 5 can function as a transient receptor for human papillomaviruses by binding virions and transferring them to adjacent cells. J Virol 80:8940–8950. https://doi.org/10.1128/JVI.00724-06
D’Souza G, Dempsey A (2011) The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med 53(Suppl 1):S5–S11. https://doi.org/10.1016/j.ypmed.2011.08.001
Daling JR, Madeleine MM, Schwartz SM et al (2002) A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 84:263–270. https://doi.org/10.1006/gyno.2001.6502
Davy CE, Jackson DJ, Wang Q et al (2002) Identification of a G(2) arrest domain in the E1 wedge E4 protein of human papillomavirus type 16. J Virol 76:9806–9818. https://doi.org/10.1128/jvi.76.19.9806-9818.2002
Day PM, Thompson CD, Schowalter RM et al (2013) Identification of a role for the trans-Golgi network in human papillomavirus 16 pseudovirus infection. J Virol 87:3862–3870. https://doi.org/10.1128/JVI.03222-12
Demeret C, Desaintes C, Yaniv M, Thierry F (1997) Different mechanisms contribute to the E2-mediated transcriptional repression of human papillomavirus type 18 viral oncogenes. J Virol 71:9343–9349. https://doi.org/10.1128/JVI.71.12.9343-9349.1997
Desaintes C, Goyat S, Garbay S et al (1999) Papillomavirus E2 induces p53-independent apoptosis in HeLa cells. Oncogene 18:4538–4545. https://doi.org/10.1038/sj.onc.1202818
Di Domenico F, Foppoli C, Blarzino C et al (2009) Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity. J Exp Clin Cancer Res 28:4. https://doi.org/10.1186/1756-9966-28-4
DiGiuseppe S, Luszczek W, Keiffer TR et al (2016) Incoming human papillomavirus type 16 genome resides in a vesicular compartment throughout mitosis. Proc Natl Acad Sci 113:6289–6294. https://doi.org/10.1073/pnas.1600638113
Dollard SC, Wilson JL, Demeter LM et al (1992) Production of human papillomavirus and modulation of the infectious program in epithelial raft cultures. OFF Genes Dev 6:1131–1142. https://doi.org/10.1101/gad.6.7.1131
Doorbar J (2013) The E4 protein; structure, function and patterns of expression. Virology 445:80–98. https://doi.org/10.1016/j.virol.2013.07.008
Doorbar J, Quint W, Banks L et al (2012) The biology and life-cycle of human papillomaviruses. Vaccine 30:F55–F70. https://doi.org/10.1016/j.vaccine.2012.06.083
Dziduszko A, Ozbun MA (2013) Annexin A2 and S100A10 regulate human papillomavirus type 16 entry and intracellular trafficking in human keratinocytes. J Virol 87:7502–7515. https://doi.org/10.1128/JVI.00519-13
Gillitzer E, Chen G, Stenlund A (2000) Separate domains in E1 and E2 proteins serve architectural and productive roles for cooperative DNA binding. EMBO J 19:3069–3079. https://doi.org/10.1093/emboj/19.12.3069
Griffin LM, Cicchini L, Pyeon D (2013) Human papillomavirus infection is inhibited by host autophagy in primary human keratinocytes. Virology 437:12–19. https://doi.org/10.1016/j.virol.2012.12.004
Guion L, Bienkowska-Haba M, DiGiuseppe S et al (2019) PML nuclear body-residing proteins sequentially associate with HPV genome after infectious nuclear delivery. PLoS Pathog 15:e1007590. https://doi.org/10.1371/journal.ppat.1007590
Harwood MC, Dupzyk AJ, Inoue T et al (2020) p120 catenin recruits HPV to γ-secretase to promote virus infection. PLoS Pathog 16:e1008946. https://doi.org/10.1371/journal.ppat.1008946
Mantovani F, Banks L (2001) The human papillomavirus E6 protein and its contribution to malignant progression. Oncogene 20:7874–7887. https://doi.org/10.1038/sj.onc.1204869
McBride AA (2013) The papillomavirus E2 proteins. Virology 445:57–79. https://doi.org/10.1016/j.virol.2013.06.006
McMurray HR, Nguyen D, Westbrook TF, McAnce DJ (2001) Biology of human papillomaviruses. Int J Exp Pathol 82:15–33. https://doi.org/10.1046/j.1365-2613.2001.00177.x
Meyers C, Frattini MG, Hudson JB, Laimins LA (1992) Biosynthesis of human papillomavirus from a continuous cell line upon epithelial differentiation. Science 257:971–973. https://doi.org/10.1126/science.1323879
Moody C (2017) Mechanisms by which HPV induces a replication competent environment in differentiating keratinocytes. Viruses 9:261. https://doi.org/10.3390/v9090261
Münger K, Basile JR, Duensing S et al (2001) Biological activities and molecular targets of the human papillomavirus E7 oncoprotein. Oncogene 20:7888–7898. https://doi.org/10.1038/sj.onc.1204860
Oh ST, Kyo S, Laimins LA (2001) Telomerase activation by human papillomavirus type 16 E6 protein: induction of human telomerase reverse transcriptase expression through Myc and GC-rich Sp1 binding sites. J Virol 75:5559–5566. https://doi.org/10.1128/JVI.75.12.5559-5566.2001
Pim D, Broniarczyk J, Siddiqa A et al (2021) Human papillomavirus 16 L2 recruits both Retromer and retriever complexes during retrograde trafficking of the viral genome to the cell nucleus. J Virol 95:e02068–e02020. https://doi.org/10.1128/JVI.02068-20
Pyeon D, Pearce SM, Lank SM et al (2009) Establishment of human papillomavirus infection requires cell cycle progression. PLoS Pathog 5:e1000318. https://doi.org/10.1371/journal.ppat.1000318
Ribeiro AL, Caodaglio AS, Sichero L (2018) Regulation of HPV transcription. Clinics (Sao Paulo) 73:e486s. https://doi.org/10.6061/clinics/2018/e486s
Richards RM, Lowy DR, Schiller JT, Day PM (2006) Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proc Natl Acad Sci U S A 103:1522–1527. https://doi.org/10.1073/pnas.0508815103
Roberts JN, Buck CB, Thompson CD et al (2007) Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan. Nat Med 13:857–861. https://doi.org/10.1038/nm1598
Rubin MA, Kleter B, Zhou M et al (2001) Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol 159:1211–1218. https://doi.org/10.1016/S0002-9440(10)62506-0
Sapp M, Day PM (2009) Structure, attachment and entry of polyoma- and papillomaviruses. Virology 384:400–409. https://doi.org/10.1016/j.virol.2008.12.022
Scheffer KD, Berditchevski F, Florin L (2014) The tetraspanin CD151 in papillomavirus infection. Viruses 6:893–908. https://doi.org/10.3390/v6020893
Selinka H-C, Giroglou T, Nowak T et al (2003) Further evidence that papillomavirus capsids exist in two distinct conformations. J Virol 77:12961–12967. https://doi.org/10.1128/JVI.77.24.12961-12967.2003
Shafti-Keramat S, Handisurya A, Kriehuber E et al (2003) Different heparan sulfate proteoglycans serve as cellular receptors for human papillomaviruses. J Virol 77:13125–13135. https://doi.org/10.1128/jvi.77.24.13125-13135.2003
Siddiqa A, Massimi P, Pim D et al (2018) Human papillomavirus 16 infection induces VAP-dependent endosomal Tubulation. J Virol 92:e01514–e01517. https://doi.org/10.1128/JVI.01514-17
Spoden G, Freitag K, Husmann M et al (2008) Clathrin- and caveolin-independent entry of human papillomavirus type 16--involvement of tetraspanin-enriched microdomains (TEMs). PLoS One 3:e3313. https://doi.org/10.1371/journal.pone.0003313
Surviladze Z, Sterk RT, DeHaro SA, Ozbun MA (2013) Cellular entry of human papillomavirus type 16 involves activation of the phosphatidylinositol 3-kinase/Akt/mTOR pathway and inhibition of autophagy. J Virol 87:2508–2517. https://doi.org/10.1128/JVI.02319-12
Thomas M, Pim D, Banks L (1999) The role of the E6-p53 interaction in the molecular pathogenesis of HPV. Oncogene 18:7690–7700. https://doi.org/10.1038/sj.onc.1202953
Venuti A, Paolini F, Nasir L et al (2011) Papillomavirus E5: the smallest oncoprotein with many functions. Mol Cancer 10:140. https://doi.org/10.1186/1476-4598-10-140
Wang JW, Roden RBS (2013) Virus-like particles for the prevention of human papillomavirus-associated malignancies. Expert Rev Vaccines 12:129–141. https://doi.org/10.1586/erv.12.151
Williams KJ, Fuki IV (1997) Cell-surface heparan sulfate proteoglycans: dynamic molecules mediating ligand catabolism. Curr Opin Lipidol 8:253–262. https://doi.org/10.1097/00041433-199710000-00003
Woodham AW, Silva DMD, Skeate JG et al (2012) The S100A10 subunit of the Annexin A2 Heterotetramer facilitates L2-mediated human papillomavirus infection. PLoS One 7:e43519. https://doi.org/10.1371/journal.pone.0043519
Xie J, Heim EN, Crite M, DiMaio D (2020) TBC1D5-catalyzed cycling of Rab7 is required for Retromer-mediated human papillomavirus trafficking during virus entry. Cell Rep 31:107750. https://doi.org/10.1016/j.celrep.2020.107750
zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350. https://doi.org/10.1038/nrc798
zur Hausen H (2009) Papillomaviruses in the causation of human cancers - a brief historical account. Virology 384:260–265. https://doi.org/10.1016/j.virol.2008.11.046
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Cruz-Gregorio, A., Aranda-Rivera, A.K. (2023). Human Papilloma Virus-Infected Cells. In: Vijayakrishnan, S., Jiu, Y., Harris, J.R. (eds) Virus Infected Cells. Subcellular Biochemistry, vol 106. Springer, Cham. https://doi.org/10.1007/978-3-031-40086-5_8
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