HPV replicative cycle and role of viral proteins in lesion progression
Ciclo replicativo do HPV e papel das proteínas virais na progressão da lesão
Palavras-chave:
Human papillomaviruses, cervical cancer, viral proteins, oncogenesisResumo
Human papillomaviruses are DNA viruses that primarily infect the stratified squamous epithelium of the genital tract mucosa. Some of these viruses are strongly associated with cervical cancer. They are sexually transmitted agents that are highly prevalent around the world. Most infections heal spontaneously, in approximately 18 to 24 months, but in some individuals, the virus persists in a latent, asymptomatic form or a productive form, causing cervical intraepithelial lesions that may progress to result in invasive cervical cancer. During productive infection, the virus executes a complex interaction program with the host cell dependent on differentiation and, through its proteins, nullifies the host cell's protective mechanisms against malignant transformation and suppresses the host's immune responses. Initial lesions may spontaneously revert, but those that reach a certain stage, if not treated, progress to malignant forms. In this review, we present some advances in the biology of HPV infection and the role of its proteins in the interaction with the host cell and its consequences.
Downloads
Referências
BAEDYANANDA, F.; SASIVIMOLRATTANA, T.; CHAIWONGKOT, A.;, VARADARAJAN, S.; BHATTARAKOSOL, P. Role of HPV16 E1 in cervical carcinogenesis. Front Cell Infect Microbiol, v. 12, p. 1–7, 2022. DOI: https://doi.org/10.3389/fcimb.2022.955847
BALAJI, D.; KALARANI, I.B.; MOHAMMED, V.; VEERABATHIRAN, R. Potential role of human papillomavirus proteins associated with the development of cancer. Virus Disease, v. 33, p. 322–333, 2022. DOI: https://doi.org/10.1007/s13337-022-00786-8
BERNARD, H. U.; BURK, R.D.; CHEN, Z.; DOORSLAER, K. VAN; HAUSEN, H. ZUR; VILLIERS, E.M. Classification of Papillomaviruses (PVs) Based on 189 PV Types and Proposal of Taxonomic Amendments. Virology, v. 401, p. 70–79, 2010. DOI: https://doi.org/10.1016/j.virol.2010.02.002
BERTI, F. C. B.; PEREIRA, A. P. L.; CEBINELLI, G. C. M.; TRUGILO, K. P.; BRAJÃO DE OLIVEIRA, K. The role of interleukin 10 in human papilloma virus infection and progression to cervical carcinoma. Cytokine Growth Factor Rev, v. 34, p. 1–13, 2017. DOI: https://doi.org/10.1016/j.cytogfr.2017.03.002
BHATTACHARJEE, R.; DAS, S. S.; BISWAL, S. S.; et al.: Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies. Crit Rev Oncol Hematol, v. 174, p. 1–17, 2022. DOI: https://doi.org/10.1016/j.critrevonc.2022.103675
BIENKOWSKA-HABA, M.; ZWOLINSKA, K.; KEIFFER, T.; SCOTT, R. S.; SAPP, M. Human Papillomavirus Genome Copy Number Is Maintained by S-Phase Amplification, Genome Loss to the Cytosol during Mitosis, and Degradation in G1 Phase. J Virol, v. 97, p. 1–21, 2023. DOI/; https://doi.org/10.1128/jvi.01879-22
BURLEY, M.; ROBERTS, S.; PARISH, J. L. Epigenetic regulation of human papillomavirus transcription in the productive virus life cycle. Semin Immunopathol, v. 42, p. 159–171, 2020. DOI: https://doi.org/10.1007/s00281-019-00773-0
CASTRO-MUÑOZ, L. J.; MANZO-MERINO, J.; MUÑOZ-BELLO, J. O.; et al.: The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response. Sci Rep, v. 9, p. 1–13, 2019. DOI: https://doi.org/10.1038/s41598-019-49886-4
CHOI, S.; ISMAIL, A.; PAPPAS-GOGOS, G.; BOUSSIOS, S. HPV and Cervical Cancer: A Review of Epidemiology and Screening Uptake in the UK. Pathogens, v. 12, p. 1–16, 2023. DOI: https://doi.org/10.3390/pathogens12020298
COSPER, P.F.; BRADLEY, S.; LUO, L.; KIMPLE, R.J. Biology of HPV Mediated Carcinogenesis and Tumor Progression. Semin Radiat Oncol, v. 31, p. 265–273, 2021. DOI: https://doi.org/10.1016/j.semradonc.2021.02.006
DELLA FERA, A. N.; WARBURTON, A.; COURSEY, T. L.; KHURANA, S.; MCBRIDE, A. A. Persistent human papillomavirus infection. Viruses, v. 13, p. 1–16, 2021. DOI: https://doi.org/10.3390/v13020321
de SANJOSÉ, S.; BROTONS, M.; PAVÓN, M.A. The natural history of human papillomavirus infection. Best Pract Res Clin Obstet Gynaecol, v. 47, p. 2–13, 2018. DOI: https://doi.org/10.1016/j.bpobgyn.2017.08.015
DIMAIO, D.; PETTI, L. The E5 Proteins. Virology, v. 445, p. 99–114, 2013. DOI: https://doi.org/10.1016/j.virol.2013.05.006
DOORBAR, J. The E4 protein; structure, function and patterns of expression. Virology, v. 445, p. 80–98, 2013. DOI: https://doi.org/10.1016/j.virol.2013.07.008
DIGIUSEPPE, S.; BIENKOWSKA-HABA, M.; GUION, L. G.; SAPP, M. Cruising the cellular highways: How human papillomavirus travels from the surface to the nucleus. Virus Res, v. 231, p. 1–9, 2017. DOI: https://doi.org/10.1016/j.virusres.2016.10.015
EGAWA, N.; WANG, Q.; GRIFFIN, H. M.; MURAKAMI, I.; JACKSON, D.; MAHMOOD, R.; DOORBAR, J. HPV16 and 18 genome amplification show different E4-dependence, with 16E4 enhancing E1 nuclear accumulation and replicative efficiency via its cell cycle arrest and kinase activation functions. PLoS Pathog, v. 13, p. 1–38, 2017. DOI: https://doi.org/10.1371/journal.ppat.1006282
EVANDE, R.; RANA, A.; BISWAS-FISS, E. E.; BISWAS, S.B. Protein–DNA Interactions Regulate Human Papillomavirus DNA Replication, Transcription, and Oncogenesis. Int J Mol Sci, v. 24, p. 1–16, 2023. DOI: https://doi.org/10.3390/ijms24108493
FINKE, J.; MIKULIČIĆ, S.; LOSTER, A. L.; GAWLITZA, A.; FLORIN, L.; LANG, T. Anatomy of a viral entry platform differentially functionalized by integrins α3 and α6. Sci Rep, v. 10, p. 1–17, 2020. DOI: https://doi.org/10.1038/s41598-020-62202-9
FONS, N. R.; KINES, R. C.; THOMPSON, C.D.; DAY, P. M.; LOWY, D. R.; SCHILLER, J. T. Chondroitin Sulfate Proteoglycans Are De Facto Cellular Receptors for Human Papillomavirus 16 under High Serum Conditions. J Virol, v. 96, p. 1–21, 2022. DOI: https://doi.org/10.1128/jvi.01857-21
GRAHAM, S. V. The human papillomavirus replication cycle, and its links to cancer progression: A comprehensive review. Clin Sci, v. 131, p. 2201–2221, 2017. DOI: https://doi.org/10.1042/CS20160786
GUTIERREZ-XICOTENCATL, L.; PEDROZA-SAAVEDRA, A.; CHIHU-AMPARAN L, SALAZAR-PIÑA A, MALDONADO-GAMA M AND ESQUIVEL-GUADARRAMA F: Cellular functions of HPV16 E5 oncoprotein during oncogenic transformation. Mol Cancer Res, v. 19, p. 167–179, 2021. DOI: https://doi.org/10.1158/1541-7786.MCR-20-0491
HARDEN, M. E.; MUNGER, K. Human papillomavirus molecular biology. Mutat Res - Rev Mutat Res, v. 772, p. 3–12, 2017. DOI: https://doi.org/10.1016/j.mrrev.2016.07.002
HARWOOD, M. C.; WOO, T. T.; TAKEO, Y.; DIMAIO, D.; TSAI, B. HPV is a cargo for the COPI sorting complex during virus entry. Sci Adv, v. 9, p. 1–18, 2023. DOI: https://doi.org/10.1126/sciadv.adc9830
HASAN, U. A.; ZANNETTI, C.; PARROCHE, P.; et al.: The Human papillomavirus type 16 E7 oncoprotein induces a transcriptional repressor complex on the Toll-like receptor 9 promoter. J Exp Med, v. 210, p. 1369–1387, 2013. DOI: https://doi.org/10.1084/jem.20122394
HOCHMANN, J.; PARIETTI, F.; MARTÍNEZ, J. et al.: Human papillomavirus type 18 e5 oncoprotein cooperates with e6 and e7 in promoting cell viability and invasion and in modulating the cellular redox state. Mem Inst Oswaldo Cruz, v. 115, p. 1–11, 2020. DOI: https://doi.org/10.1590/0074-02760190405
HU, L; POTAPOVA, T. A.; LI, S.; RANKIN, S.; GORBSKY, G. J.; ANGELETTI, P. C.; CERESA, B. P. Expression of HPV16 E5 produces enlarged nuclei and polyploidy through endoreplication. Virology, v. 405, p. 342–351, 2010. DOI: https://doi.org/10.1016/j.virol.2010.06.025
JIANG, P.; YUE, Y. Human papillomavirus oncoproteins and apoptosis (Review). Exp Ther Med, v. 7, p. 3–7, 2014. DOI: https://doi.org/10.3892/etm.2013.1374
KADAJA, M.; SILLA, T.; USTAV, E.; USTAV, M. Papillomavirus DNA replication - From initiation to genomic instability. Virology, v. 384, p. 360–368, 2009. DOI: https://doi.org/10.1016/j.virol.2008.11.032
KALITERNA, V.; BARISIC, Z. Genital human papillomavirus infections. Front Biosci - Landmark, v. 23, p. 1587–1611, 2018. DOI: https://doi.org/10.2741/4662
KHALIL, M. I.; YANG, C.; VU, L.; et al.: HPV upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer. PLoS Pathog, v. 19, p. 1–28, 2023. DOI: https://doi.org/10.1371/journal.ppat.1011171
KHURANA, S.; MARKOWITZ, T. E.; KABAT, J.; MCBRIDE, A. A. Spatial and Functional Organization of Human Papillomavirus Replication Foci in the Productive Stage of Infection. MBio, v. 12, p. 1–23, 2021. DOI: https://doi.org/10.1128/mBio.02684-21
LAI, K.Y. et al. A ran-binding protein facilitates nuclear import of human papillomavirus type 16. PLoS Pathogens, v. 17, n.5, p. 1–26, 2021. DOI: https://doi.org/10.1371/journal.ppat.1009580
LI, Y.; XU, C. Human papillomavirus-related cancers. Adv Exp Med Biol, v. 1018, p. 23–34, 2017. DOI: https://doi.org/10.1007/978-981-10-5765-6_3
LIU, H; XU J, YANG Y, et al. Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1. Proc Natl Acad Sci U S A, v. 118, p. 1–12, 2021. DOI: https://doi.org/10.1073/pnas.2014195118
LIU, X.; DAKIC, A.; ZHANG, Y.; DAI, Y.; CHEN, R.; SCHLEGEL, R. HPV E6 protein interacts physically and functionally with the cellular telomerase complex. Proc Natl Acad Sci U S A, v. 106, p. 18780–18785, 2009. DOI: https://doi.org/10.1073/pnas.0906357106
MALIK, S.; SAH, R.; MUHAMMAD, K.; WAHEED, Y. Tracking HPV Infection, Associated Cancer Development, and Recent Treatment Efforts—A Comprehensive Review. Vaccines, v. 11, p. 1–16, 2023. DOI: https://doi.org/10.3390/vaccines11010102
MCKINNEY, C. C.; HUSSMANN, K. L.; MCBRIDE, A. A. The role of the DNA damage response throughout the papillomavirus life cycle. Viruses, v. 7, p. 2450–2469, 2015. DOI: https://doi.org/10.3390/v7052450
MCLAUGHLIN-DRUBIN, M. E.; MÜNGER, K. The Human Papillomavirus E7 Oncoprotein. Virology, v. 384, p. 335–344, 2009. DOI: https://doi.org/10.1016/j.virol.2008.10.006
MIYAUCHI S, KIM SS, JONES RN, et al.: Human papillomavirus E5 suppresses immunity via inhibition of the immunoproteasome and STING pathway. Cell Rep, v. 42, 1–20, 2023. DOI: https://doi.org/10.1016/j.celrep.2023.112508
MOODY, C. A.; LAIMINS, L.A. Human papillomavirus oncoproteins: Pathways to transformation. Nat Rev Cancer, v. 10, p. 550–560, 2010. DOI: https://doi.org/10.1038/nrc2886
MOODY, C.A. Mechanisms by which HPV induces a replication competent environment in differentiating keratinocytes. Viruses, v. 9, p. 1–21, 2017. DOI: https://doi.org/10.3390/v9090261
NTANASIS-STATHOPOULOS, I.; KYRIAZOGLOU, A; LIONTOS, M; DIMOPOULOS, M.A.; GAVRIATOPOULOU, M. Current trends in the management and prevention of human papillomavirus (HPV) infection. J buon, v. 25, p. 1281–1285, 2020. https://www.jbuon.com/archive/25-3-1281.pdf
OH, J. M.; KIM, S. H.; CHO, E. A.; SONG, Y. S.; KIM, W. H.; JUHNN, Y. S. Human papillomavirus type 16 E5 protein inhibits hydrogen peroxide-induced apoptosis by stimulating ubiquitin-proteasome-mediated degradation of Bax in human cervical cancer cells. Carcinogenesis, v. 31, p. 402–410, 2010. DOI: https://doi.org/10.1093/carcin/bgp318
PAN, W.; WANG, S.; LIU, X.; et al.: KNTC1, regulated by HPV E7, inhibits cervical carcinogenesis partially through Smad2. Exp Cell Res, v. 423, p. 113458, 2023. DOI: https://doi.org/10.1016/j.yexcr.2023.113458
PAPPA, K. I.; KONTOSTATHI, G.; LYGIROU, V.; ZOIDAKIS, J.; ANAGNOU, N. P. Novel structural approaches concerning HPV proteins: Insight into targeted therapies for cervical cancer (Review). Oncol Rep, v. 39, p. 1547–1554, 2018. DOI: https://doi.org/10.3892/or.2018.6257
PRABHAKAR, A. T.; JAMES, C. D.; FONTAN, C. T. et al. Human Papillomavirus 16 E2 Interaction with TopBP1 Is Required for E2 and Viral Genome Stability during the Viral Life Cycle. J Virol, v. 97, p. 1–19, 2023. DOI: https://doi.org/10.1128/jvi.00063-23
PRZYBYLSKI, M.; PRUSKI, D.; WSZOŁEK, K.; DE MEZER, M.; ŻURAWSKI, J.; JACH, R.; MILLERT-KALIŃSKA, S: Prevalence of HPV and Assessing Type-Specific HPV Testing in Cervical High-Grade Squamous Intraepithelial Lesions in Poland. Pathogens, v. 12, p. 1–10, 2023. DOI: https://doi.org/10.3390/pathogens12020350
RAMOS DA SILVA, J.; BITENCOURT RODRIGUES, K.; FORMOSO PELEGRIN, G.; et al. Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice. Sci Transl Med, v. 15, p. 1–18, 2023. DOI: https://doi.org/10.1126/scitranslmed.abn3464
ROMAN, A.; MUNGER, K. The papillomavirus E7 proteins. Virology, v. 445, p. 138–168, 2013. DOI: https://doi.org/10.1016/j.virol.2013.04.013
SCHIFFMAN, M.; DOORBAR, J.; WENTZENSEN, N. et al.: Carcinogenic human papillomavirus infection. Nat Rev Dis Prim, v. 2, p. 1–20, 2016. DOI: https://doi.org/10.1038/nrdp.2016.86
SCHILLER, J. T.; LOWY, D. R. Understanding and learning from the success of prophylactic human papillomavirus vaccines. Nat Rev Microbiol, v. 10, p. 681–692, 2012. DOI: https://doi.org/10.1038/nrmicro2872
SCHUCK, S.; STENLUND, A. A Conserved Regulatory Module at the C Terminus of the Papillomavirus E1 Helicase Domain Controls E1 Helicase Assembly. J Virol, v. 89, p. 1129–1142, 2015. DOI: https://doi.org/10.1128/jvi.01903-14
SONGOCK, W. K.; KIM, S.; BODILY, J. M. The human papillomavirus E7 oncoprotein as a regulator of transcription. Virus Res, v. 231, p. 56–75, 2017. DOI: https://doi.org/10.1016/j.virusres.2016.10.017
STUDSTILL, C. J.; MOODY, C.A. For Better or Worse: Modulation of the Host DNA Damage Response by Human Papillomavirus. Annu Rev Virol, v. 10, p. 325–345, 2023. DOI: https://doi.org/10.1146/annurev-virology-111821-103452
TAGUCHI, A.; NAGASAKA, K.; PLESSY, C., et al. Use of Cap Analysis Gene Expression to detect human papillomavirus promoter activity patterns at different disease stages. Sci Rep, v. 10, p. 1–10, 2020. DOI: https://doi.org/10.1038/s41598-020-75133-2
THATTE, J.; MASSIMI, P.; THOMAS, M.; BOON, S. S.; BANKS, L. The Human Papillomavirus E6 PDZ Binding Motif Links DNA Damage Response Signaling to E6 Inhibition of p53 Transcriptional Activity. J Virol, v. 92, p. 1–14, 2018. DOI: https://doi.org/10.1128/jvi.00465-18
TOMITA, T.; HUIBREGTSE, J. M.; MATOUSCHEK, A. A masked initiation region in retinoblastoma protein regulates its proteasomal degradation. Nat Commun, v. 11, p. 1–8, 2020. DOI: https://doi.org/10.1038/s41467-020-16003-3
VAN DOORSLAER, K.; DESALLE, R.; EINSTEIN, M. H.; BURK, R. D. Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche. PLoS Pathog, v. 11, p. 1–14, 2015. DOI: https://doi.org/10.1371/journal.ppat.1004980
VIVEROS-CARREÑO, D.; FERNANDES, A.; PAREJA, R: Updates on cervical cancer prevention. Int J Gynecol Cancer, v. 33, p. 394–402, 2023. DOI: https://doi.org/10.1136/ijgc-2022-003703
WALLACE, N. A.; GALLOWAY, D. A. Novel Functions of the Human Papillomavirus E6 Oncoproteins. Annu Rev Virol, v. 2, p. 403–423, 2015. DOI: https://doi.org/10.1146/annurev-virology-100114-055021
WANG, J.W.; RODEN, R.B.S. L2, the minor capsid protein of papillomavirus. Virology, v. 445, p. 175–186, 2013. DOI: https://doi.org/10.1016/j.virol.2013.04.017
WANG, J.; et al. YY1 Positively Regulates Transcription by Targeting Promoters and Super-Enhancers through the BAF Complex in Embryonic Stem Cells. Stem Cell Reports, v. 10, n. 4, p. 1324-1339. DOI: https://doi.org/10.1016/j.stemcr.2018.02.004
WAROWICKA, A.; BRONIARCZYK, J.; WĘGLEWSKA, M.; KWAŚNIEWSKI, W.; GOŹDZICKA-JÓZEFIAK A. Dual Role of YY1 in HPV Life Cycle and Cervical Cancer Development. Int J Mol Sci, v. 23, n. 7, 3453. DOI: https://doi.org/10.3390/ijms23073453
WASSON, C. W.; MORGAN, E. L.; MÜLLER, M.; ROSS, R. L.; HARTLEY, M.; ROBERTS, S.; MACDONALD, A. Human papillomavirus type 18 E5 oncogene supports cell cycle progression and impairs epithelial differentiation by modulating growth factor receptor signalling during the virus life cycle. Oncotarget, v. 8, p. 103581–103600, 2017. DOI: https://doi.org/10.18632/oncotarget.21658
YAJID, A.I.; ZAKARIAH, M. A.; ZIN, A. A. M.; OTHMAN, N.H. Potential role of E4 protein in human papillomavirus screening: A review. Asian Pacific J Cancer Prev, v. 18, p. 315–319, 2017. DOI: https://doi.org/10.22034/APJCP.2017.18.2.315
ZHI, W.; WEI, Y.; LAZARE, C.; et al.: HPV-CCDC106 integration promotes cervical cancer progression by facilitating the high expression of CCDC106 after HPV E6 splicing. J Med Virol, v. 95, p. 1–11, 2023. DOI: https://doi.org/10.1002/jmv.28009
ZHU, H.; SHEN, Z.; LUO, H.; ZHANG, W.; ZHU, X: Chlamydia trachomatis infection-associated risk of cervical cancer: A meta-analysis. Med (United States), v. 95, p. 1–10, 2016. DOI: https://doi.org/10.1097/md.0000000000003077