The mouse papillomavirus epigenetic signature is characterised by DNA hypermethylation after lesion regression

Tschirley, Allison; Stockwell, Peter A.; Rodger, Euan J.; Eltherington, Oliver; Morison, Ian M.; Christensen, Neil D.; Chatterjee, Aniruddha; Hibma, Merilyn

doi:10.1101/2021.04.19.440429

2021

DOI: 10.1101/2021.04.19.440429

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The mouse papillomavirus epigenetic signature is characterised by DNA hypermethylation after lesion regression

Allison Tschirley

Peter A. Stockwell

Euan J. Rodger

et al.

Abstract: The β genus of human papillomaviruses (HPVs) infect cutaneous epidermis. They contribute to the development of cutaneous squamous cell carcinoma (cSCC) in individuals with epidermodysplasia verruciformis, and increase susceptibility to UV-induced cSCC. This has been demonstrated in UV-exposed mice previously infected with mouse papillomavirus (MmuPV1). However, the mechanism by which β-HPVs contribute to cSCC is unclear. We propose that viral infection leaves a DNA methylation signature following resolution of… Show more

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A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus

King

Bilger

Rademacher

et al. 2022

Viruses

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Recurrent respiratory papillomatosis (RRP), caused by laryngeal infection with low-risk human papillomaviruses, has devastating effects on vocal communication and quality of life. Factors in RRP onset, other than viral presence in the airway, are poorly understood. RRP research has been stalled by limited preclinical models. The only known papillomavirus able to infect laboratory mice, Mus musculus papillomavirus (MmuPV1), induces disease in a variety of tissues. We hypothesized that MmuPV1 could infect the larynx as a foundation for a preclinical model of RRP. We further hypothesized that epithelial injury would enhance the ability of MmuPV1 to cause laryngeal disease, because injury is a potential factor in RRP and promotes MmuPV1 infection in other tissues. In this report, we infected larynges of NOD scid gamma mice with MmuPV1 with and without vocal fold abrasion and measured infection and disease pathogenesis over 12 weeks. Laryngeal disease incidence and severity increased earlier in mice that underwent injury in addition to infection. However, laryngeal disease emerged in all infected mice by week 12, with or without injury. Secondary laryngeal infections and disease arose in nude mice after MmuPV1 skin infections, confirming that experimentally induced injury is dispensable for laryngeal MmuPV1 infection and disease in immunocompromised mice. Unlike RRP, lesions were relatively flat dysplasias and they could progress to cancer. Similar to RRP, MmuPV1 transcript was detected in all laryngeal disease and in clinically normal larynges. MmuPV1 capsid protein was largely absent from the larynx, but productive infection arose in a case of squamous metaplasia at the level of the cricoid cartilage. Similar to RRP, disease spread beyond the larynx to the trachea and bronchi. This first report of laryngeal MmuPV1 infection provides a foundation for a preclinical model of RRP.

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A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus

King

Bilger

Rademacher

et al. 2022

Viruses

View full text Add to dashboard Cite

show abstract

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The mouse papillomavirus epigenetic signature is characterised by DNA hypermethylation after lesion regression

Cited by 1 publication

References 54 publications

A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus

A Novel In Vivo Model of Laryngeal Papillomavirus-Associated Disease Using Mus musculus Papillomavirus

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