Expression of Human papillomavirus type 52 L1 capsid gene in Oryza sativa involved in cytoprotective activities
Keywords:cervical cancer; Human papillomavirus; Oryza sativa; plant vaccine; type 52 L1 capsid protein
Female cervical cancer is largely formed by Human papillomavirus (HPV), the second leading cause of cancer deaths in women worldwide. HPV-52 is a regionally common high-risk type of cervical cancer found mostly in Asia and reveals geographical variations, in order of importance, as types HPV-16 and -18. However, the differing propensities of HPV types in progressing to cancer, focusing on HPV-52 vaccines, are limited. Several plant-based vaccines against cancer have been developed, and the production of candidate HPV therapeutic vaccines using plant-derived expression platforms is also proven. The objectives of this study were to assess the HPV-52L1 Capsid gene by transferring HPV-52L1 Capsid cDNA into rice (Oryza sativa L.) via an Agrobacterium-mediated transformation, and accumulating HPV-52L1 Capsid proteins in a plant-based expression system to maintain and improve antigenicity. Crude protein extracts containing 5~20 μg from OsHP-52L1 transgenic lines induced cell death and significantly reduced cell proliferation in HPV-positive HeLa cervical cancer cells compared with those non-transformant (NT) rice plants. However, no significant cytotoxicity of induced human breast MDA-MB-231 cell proliferation (as negative control) was observed at any dose compared with NT groups. HeLa cells ameliorated the effects of OsHPV crude protein extracts on cell viability as the extract concentration increased, and treatment with 20 μg of the extract from OsHPV-3 significantly reduced cell viability in HeLa cells (26%) compared with the control group (57%). Our results can be used for exploring the potential of plants for increasing the immunogenicity of OsHPV-52L1 Capsid DNA vaccines, and support the development of cost-effective HPV vaccines, which is highly desirable for resource-poor countries.
Bryan JT, Brownlow MK, Schultz LD, Jansen KU (2010). U.S. Patent No. 7,700,103. Washington, DC: U.S. Patent and Trademark Office.
Cardona CE, García-Perdomo HA (2018). Incidence of penile cancer worldwide: systematic review and meta-analysis. Revista Panamericana de Salud Publica 41:e117.
Chabeda A, Yanez R, Lamprecht R, Meyers A, Rybicki E, Hitzeroth I (2018). Therapeutic vaccines for high-risk HPV-associated diseases. Papillomavirus Research 5:46-58.
Chiang CM, Chen CC, Chen SP, Lin, KH, Chen LR, Su YH, Yen HC (2017). Overexpression of the ascorbate peroxidase gene from eggplant and sponge gourd enhances flood tolerance in transgenic Arabidopsis. Journal of Plant Research 130(2):373-386.
Chen X, Zhang T, Liu H, Hao Y, Liao G, Xu X (2018). Displaying 31RG-1 peptide on the surface of HPV16 L1 by use of a human papillomavirus chimeric virus-like particle induces cross-neutralizing antibody responses in mice. Human Vaccines and Immunotherapeutics 14(8):2025-2033.
Conway M, Meyers C (2009). Replication and assembly of human papillomaviruses. Journal of Dental Research 88:307-317.
Cordeiro MN, De Lima RC, Paolini F, Melo AR, Campos AP, Venuti A (2018). Current research into novel therapeutic vaccines against cervical cancer. Expert Review of Anticancer Therapy 18:365-376.
De la Rosa GP, A Monroy-García, ML Mora-García, CG Peña, J Hernández-Montes, B Weiss-Steider, MA Lim (2009). An HPV 16 L1-based chimeric human papilloma virus-like particles containing a string of epitopes produced in plants is able to elicit humoral and cytotoxic T-cell activity in mice. Virology Journal 6:2.
De Buck S, Windelsb P, De Looseb M, Depicker A (2004). Single copy T-DNAs integrated at different positions in the Arabidopsis genome display uniform and comparable β-glucuronidase accumulation levels. Cellular and Molecular Life Sciences 61(19-20):2632-2645.
de Villiers EM, Fauquet, C, Broker, TR, Bernard, H.U, Zur HH (2004). Classification of papillomaviruses. Virology 324:17-27.
Doyle JJ, Doyle JL (1990). Isolation of plant DNA from fresh tissue. Focus 12:13-15.
Fernandez-San MA, Ortigosa SM, Hervas-Stubbs S (2008). Human papillomavirus L1 protein expressed in tobacco chloroplasts self-assembles into virus-like particles that are highly immunogenic. Plant Biotechnology Journal 6:427-441.
Franconi R, Massa S, Illiano E (2006). Exploiting the plant secretory pathway to improve the anticancer activity of a plant derived HPV16 E7 vaccine. International Journal of Immunopathology and Pharmacology 19:187-197.
Franconi R, Demurtas OC, Massa S (2010). Plant-derived vaccines and other therapeutics produced in contained systems. Expert Review of Vaccines 9(8):877-892.
García-Piñeres AJ, Hildesheim A, Dodd L, Kemp TJ, Yang J, Fullmer B, Pinto LA (2009). Gene expression patterns induced by HPV-16 L1 virus-like particles in leukocytes from vaccine recipients. The Journal of Immunology 182:1706-1729.
Gansukh E, Mya KK, Jung M, Keum YS, Kim DH, Saini RK (2019). Lutein derived from marigold (Tagetes erecta) petals triggers ROS generation and activates Bax and caspase-3 mediated apoptosis of human cervical carcinoma (HeLa) cells. Food and Chemical Toxicology 127:11-18.
Hefferon K (2017). Plant virus expression vectors: a powerhouse for global health. Biomedicines 5:44.
Hassan S W, MT Waheed, M Muller, JL Clarke, ZK Shinwari, AG Lossl (2014). Expression of HPV-16 L1 capsomeres with glutathione-S-transferase as a fusion protein in tobacco plastids: An approach for a capsomerebased HPV vaccine. Human Vaccines and Immunotherapeutics 10(10):2975-2982.
Hsing YI, Chern CG, Fan MJ, Lu PC, Chen KT, Lo SF, … Lee KW (2007). A rice gene activation/knockout mutant resource for high throughput functional genomics. Plant Molecular Biology 63(3):351-364.
Huh WK, Joura EA., Giuliano AR, Iversen, OE, de Andrade RP, Ault KA (2017). Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16–26 years: A randomised, double-blind trial. Lancet 390:2143-2159.
Kaliamurthi S, Selvaraj G, Kaushik AC, Gu KR, Wei DQ (2018). Designing of CD8+ and CD8+-overlapped CD4+ epitope vaccine by targeting late and early proteins of human papillomavirus. Biologics Targets Therapy 12:107.
Kim SI, Veena SB, Gelvin SB (2007). Genome-wide analysis of Agrobacterium T-DNA integration sites in the Arabidopsis genome generated under non-selective conditions. The Plant Journal 51:779-791.
Kines RC, Thompson CD, Lowy DR, Schiller JT, Day PM (2009). The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding. Proceedings of the National Academy of Science 106:20458-20463.
Kohl T, Hitzeroth I, Stewart D (2006). Plant-produced cottontail rabbit papillomavirus L1 protein protects against tumor challenge: a proof-of-concept study. Clinical Vaccine and Immunology 13:845-853.
Kohl T, Hitzeroth I, Christensen N, Rybicki E (2007). Expression of HPV-11L1 protein in transgenic Arabidopsis thaliana and Nicotiana tabacum. BMC Biotechnology 7(1):56.
Karanam B, Subhashini J, WK Huh, Roden RB (2009). Developing vaccines against minor capsid antigen L2 to prevent papillomavirus infection. Immunology and Cell Biology 87:287-299.
Lamprecht RL, Kennedy P., Huddy SM, Bethke S, Hendrikse M., Hitzeroth II, Rybicki EP (2016). Production of Human papillomavirus pseudovirions in plants and their use in pseudovirion-based neutralisation assays in mammalian cells. Scientific Reports 6:20431.
Liao YD, Lin KH, Chen CC, Chiang CM (2016). Oryza sativa protein phosphatase 1a (OsPP1a) involved in salt stress tolerance in transgenic rice. Molecular Breeding 36:22.
Loh H S, Green, BJ, Yusibov V (2017). Using transgenic plants and modified plant viruses for the development of treatments for human diseases. Current Opinion in Virology 26:81-89.
Massa S, Presenti O, Benvenuto E (2018). Engineering plants for the future: farming with value-added harvest. In: Progress in Botany 80:65-108.
Massa S, Paolini F, Marino C, Franconi R, Venuti A (2019). Bioproduction of a therapeutic vaccine against human papillomavirus in tomato hairy root cultures. Frontiers in Plant Science 10:452.
Naphatsamon U, Ohashi T, Misaki R, Fujiyama K (2018). The production of human β-glucocerebrosidase in Nicotiana benthamiana root culture. International Journal of Molecular Sciences 19(7):E1972.
Naud PS, Roteli-Martins CM, De Carvalho N, Teixeira JC, de Borba PC, Sanchez N (2014). Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination. Human Vaccines and Immunotherapeutics 10:2147-2162.
Parkin DM, F Bray (2006). The burden of HPV-related cancers. Vaccine 24:S1-S25.
Parkin D, Maxwell S, Louie S, Clifford G (2008). Burden and trends of type-specific human papillomavirus infections and related diseases in the Asia Pacific Region. Vaccine 26:L1-L15.
Peng S, Qiu J, Yang A, Yang B, Wang JW (2016). Optimization of heterologous DNA-prime, protein boost regimens and site of vaccination to enhance therapeutic immunity against human papillomavirus-associated disease. Cell and Bioscience 6(1):16.
Pineo CB, Hitzeroth II, Rybicki EP (2013). Immunogenic assessment of plant-produced human papillomavirus type 16 L1/L2 chimaeras. Plant Biotechnology Journal 11:964-975.
Roden RB, Stern PL (2018). Opportunities and challenges for human papillomavirus vaccination in cancer. Nature Reviews Cancer 18:240-254.
Santos RB, Abranches R, Fischer R, Sack M, Holland T (2016). Putting the spotlight back on plant suspension cultures. Frontiers in Plant Science 7:60-72.
Schug Z, Peck B, Jones D, Zhang Q, Alam I, Witney T, Aboagye E (2014). Acetyl-coA synthetase 2 promotes acetate utilization and maintains cell growth under metabolic stress. Cancer Cell 27(1):57-71.
Schellenbacher C, Richard R, and R Kirnbauer (2017). Developments in L2-based Human Papillomavirus (HPV) Vaccines. Virus Research 231:166-175.
Šmídková MM, Müller N, Thönes K, Piuko P, Angelisová J, Velemínský KJ (2010). Angelis. Transient expression of human papillomavirus type 16 virus-like particles in tobacco and tomato using a tobacco rattle virus expression vector. Biologia Plantarum 54:451-460.
Suhandono S, Ungu DAK, Kristianti T, Sahiratmadja E, Susanto H (2014) Cloning, expression and bioinformatic analysis of human papillomavirus type 52 L1 capsid gene from Indonesian patient. Microbiology Indonesia 8:2.
Venuti A, G Curzio, L Mariani, F Paolini (2015). Immunotherapy of HPV-associated cancer: DNA/plant-derived vaccines and new orthotopic mouse models. Cancer Immunology and Immunotherapy 64:1329-1338.
Vici P, Pizzuti L, Mariani L, Zampa G, Santini D, Di Lauro L (2016). Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: Hope or reality from clinical studies. Expert Review of Vaccines 15:1327-1336.
Wang Y, Miao J, Chard L, Wang Z (2019). Syrian hamster as an animal model for the study on infectious diseases. Frontiers Immunology 10:2329.
Wang W, Vignani R, Scali M, Cresti M (2006). An universal and rapid protocol for protein extraction from recalcitrant plant tissues for proteomic analysis. Electrophoresis 27:2782-2786.
Wong-Arce A, González-Ortega O, Rosales-Mendoza S (2017). Plant-made vaccines in the fight against cancer. Trends in Biotechnology 35:241-256.
Warzecha H, Mason HS, Lane C (2003). Oral immunogenicity of human papillomavirus-like particles expressed in potato. Journal of Virology 77:8702-8711.
How to Cite
Open Access Journal:
The journal allows the author(s) to retain publishing rights without restriction. Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author.