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Review
. 2022 Sep 4;14(9):1964.
doi: 10.3390/v14091964.

Modeling HPV-Associated Disease and Cancer Using the Cottontail Rabbit Papillomavirus

Nancy M Cladel  1   2 , Jie Xu  3 , Xuwen Peng  4 , Pengfei Jiang  5 , Neil D Christensen  1   2   6 , Zhi-Ming Zheng  7 , Jiafen Hu  1   2
Affiliations
Review

Modeling HPV-Associated Disease and Cancer Using the Cottontail Rabbit Papillomavirus

Nancy M Cladel et al. Viruses. .

Abstract

Approximately 5% of all human cancers are attributable to human papillomavirus (HPV) infections. HPV-associated diseases and cancers remain a substantial public health and economic burden worldwide despite the availability of prophylactic HPV vaccines. Current diagnosis and treatments for HPV-associated diseases and cancers are predominantly based on cell/tissue morphological examination and/or testing for the presence of high-risk HPV types. There is a lack of robust targets/markers to improve the accuracy of diagnosis and treatments. Several naturally occurring animal papillomavirus models have been established as surrogates to study HPV pathogenesis. Among them, the Cottontail rabbit papillomavirus (CRPV) model has become known as the gold standard. This model has played a pivotal role in the successful development of vaccines now available to prevent HPV infections. Over the past eighty years, the CRPV model has been widely applied to study HPV carcinogenesis. Taking advantage of a large panel of functional mutant CRPV genomes with distinct, reproducible, and predictable phenotypes, we have gained a deeper understanding of viral-host interaction during tumor progression. In recent years, the application of genome-wide RNA-seq analysis to the CRPV model has allowed us to learn and validate changes that parallel those reported in HPV-associated cancers. In addition, we have established a selection of gene-modified rabbit lines to facilitate mechanistic studies and the development of novel therapeutic strategies. In the current review, we summarize some significant findings that have advanced our understanding of HPV pathogenesis and highlight the implication of the development of novel gene-modified rabbits to future mechanistic studies.

Keywords: CRPV; HPV; RNAseq; cancer; codon optimization; disease progression; gene modified rabbits; immune responses; papillomavirus; rabbit; tumor regression; wound healing.

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Conflict of interest statement

All authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Several milestones of the CRPV rabbit model (blue) and HPV study (red). The rabbit model has played a pivotal role in HPV vaccine development and better understanding of HPV pathogenesis. The research using the rabbit model can be divided into two periods based on the first report on the genomic sequence of CRPV: pre-genetic modification era and post-genetic modification era. The notable research activities on the rabbit model have continued to reduce over the last two decades.
Figure 2
Figure 2
The CRPV rabbit model mimics HPV-associated infections and diseases with predictable disease outcomes at different time frames. Significant immune cell infiltrates (yellow arrows) were found in the tumors undergoing regression.
See this image and copyright information in PMC

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References

    1. Roden R.B.S., Stern P.L. Opportunities and challenges for human papillomavirus vaccination in cancer. Nat. Rev. Cancer. 2018;18:240–254. doi: 10.1038/nrc.2018.13. - DOI - PMC - PubMed
    1. Doorbar J. Host control of human papillomavirus infection and disease. Best Pract. Res. Clin. Obstet. Gynaecol. 2018;47:27–41. doi: 10.1016/j.bpobgyn.2017.08.001. - DOI - PubMed
    1. Christensen N.D., Budgeon L.R., Cladel N.M., Hu J. Recent advances in preclinical model systems for papillomaviruses. Virus Res. 2017;231:108–118. doi: 10.1016/j.virusres.2016.12.004. - DOI - PMC - PubMed
    1. Shope R.E., Hurst E.W. Infectious papillomatosis of rabbits; with a note on the histopathology. J. Exp. Med. 1933;58:607–624. doi: 10.1084/jem.58.5.607. - DOI - PMC - PubMed
    1. Escudero Duch C., Williams R.A., Timm R.M., Perez-Tris J., Benitez L. A Century of Shope Papillomavirus in Museum Rabbit Specimens. PLoS ONE. 2015;10:e0132172. doi: 10.1371/journal.pone.0132172. - DOI - PMC - PubMed

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