Expression of Human papillomavirus type 52 L1 capsid gene in Oryza sativa involved in cytoprotective activities

Kuan-Hung Lin,Shwu-Fen Pan,Chiu-Chen Chen,Wen-Shian Li,Chih-Ming Chiang

doi:10.15835/nbha48111750

Abstract

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.

Highlights

Human papillomavirus (HPV) related cancers account for 5% of all human cancers (Chabeda et al, 2018)
In an attempt to produce a valid immunotherapy at low cost for HPV-associated lesion/cancer, our study focused on the development of low-cost platforms such as DNA and plant biotechnologies
Crude protein extracts from Oryza sativa Human papillomavirus (OsHPV)-52L1 transgenic lines with 5, 10, 15, and 20 μg concentrations effectively inhibited human HeLa cell proliferation

Summary

Introduction

Human papillomavirus (HPV) related cancers account for 5% of all human cancers (Chabeda et al, 2018). Available preventive vaccines against HPV are based on VLPs prepared by the recombinant expression and assembly of L1, and different types of prophylactic vaccines based on the immune-dominant L protein are currently on the market and are effective in preventing cervical disease (Naud et al, 2014; Huh et al, 2017). HPV infection is preventable through very efficient recombinant vaccines developed against variously incident oncogenic genotypes in yeast and insect cells, and despite cervical cytology and DNA testing, HPV-related preinvasive and invasive diseases remain critical public health problems. Currently available treatments against HPV-related disease are only moderately successful, with radiotherapy, chemotherapy, and surgery being very poorly efficient against high-grade lesions (Cordeiro et al, 2018)

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