A Comparative Study on Delivery of Externally Attached DNA by Papillomavirus VLPs and Pseudoviruses.

Sarah Brendle,Neil Christensen,Karla Balogh,Samina Alam,Nancy Cladel,Jiafen Hu,Craig Meyers

doi:10.3390/vaccines9121501

Sarah Brendle, Neil Christensen + Show 5 more

Open Access

https://doi.org/10.3390/vaccines9121501

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Journal: Vaccines	Publication Date: Dec 18, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Pennsylvania State University

Abstract

Human papillomavirus (HPV) 16 capsids have been chosen as a DNA delivery vehicle in many studies. Our preliminary studies suggest that HPV58 capsids could be better vehicles than HPV16 capsids to deliver encapsidated DNA in vitro and in vivo. In the current study, we compared HPV16, HPV58, and the cottontail rabbit papillomavirus (CRPV) capsids either as L1/L2 VLPs or pseudoviruses (PSVs) to deliver externally attached GFP-expressing DNA. Both rabbit and human cells were used to test whether there was a species-specific effect. DNA delivery efficiency was determined by quantifying either GFP-expressing cell populations or mean fluorescent intensities (MFI) by flow cytometry. Interestingly, CRPV and 58-VLPs and PSVs were significantly more efficient at delivering attached DNA when compared to 16-VLPs and PSVs. A capsid/DNA ratio of 2:1 showed the highest efficiency for delivering external DNA. The PSVs with papillomavirus DNA genomes also showed higher efficiency than those with irrelevant plasmid DNA. HPV16L1/58L2 hybrid VLPs displayed increased efficiency compared to HPV58L1/16L2 VLPs, suggesting that L2 may play a critical role in the delivery of attached DNA. Additionally, we demonstrated that VLPs increased in vivo infectivity of CRPV DNA in rabbits. We conclude that choosing CRPV or 58 capsids to deliver external DNA could improve DNA uptake in in vitro and in vivo models.

Highlights

Our preliminary study demonstrated that HPV58 capsids containing the cottontail rabbit papillomavirus (CRPV) DNA genome showed higher infectivity when compared with corresponding HPV16 capsids
We found that the L1 and L2 interaction between hybrid HPV16 and HPV58 L1/L2 virus-like particles (VLPs) was not interrupted in terms of capsid formation and encapsidating DNA
Our study demonstrated that HPV58 and CRPV capsids are advantageous to HPV16 for delivering attached DNA, and the delivery efficacy is L2-dependent

Summary

Introduction

Papillomavirus capsids comprise a major capsid protein, L1, and a minor capsid protein, L2 [1,2]. Papillomavirus virus-like particles (VLPs) can be produced from L1 only or L1 and L2 [3]. L1 VLPs have been developed into successful prophylactic vaccines for the control of several human papillomavirus-induced diseases and cancers [4,5]. Papillomavirus L1 VLPs have been shown to bind to several different species of cells and cell types and be internalized by these same cells; [6,7], they are potential vehicles to deliver encapsidated DNA. A previous study suggested that L1/L2 VLPs were more efficient for DNA delivery than L1 VLPs, suggesting that L2 positively impacted the delivery [8]

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