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

Area of Science:

• Oncology
• Virology
• Genetics

Background:

• Human papillomavirus (HPV) causes approximately 5% of human cancers, posing a significant global health burden.
• Current HPV diagnosis and treatment lack robust molecular targets, relying on morphological examination and high-risk HPV typing.
• Animal papillomavirus models are crucial for studying HPV pathogenesis, with the Cottontail rabbit papillomavirus (CRPV) model being a gold standard.

Purpose of the Study:

• To review significant findings from the CRPV model that enhance understanding of HPV pathogenesis.
• To highlight the utility of gene-modified rabbits for mechanistic studies and therapeutic development in HPV-associated cancers.

Main Methods:

• Utilizing a panel of functional mutant CRPV genomes to study viral-host interactions during tumor progression.
• Applying genome-wide RNA-seq analysis to the CRPV model to identify molecular changes relevant to HPV-associated cancers.
• Establishing gene-modified rabbit lines for in-depth mechanistic investigations.

Main Results:

• The CRPV model has provided key insights into HPV carcinogenesis over 80 years.
• RNA-seq analysis in the CRPV model has validated molecular changes mirroring those in human HPV cancers.
• Gene-modified rabbits facilitate the study of viral pathogenesis and the exploration of novel therapeutic strategies.

Conclusions:

• The CRPV model is instrumental in advancing the understanding of HPV pathogenesis and carcinogenesis.
• Gene-modified rabbits represent a powerful tool for future research into HPV-associated diseases and the development of innovative treatments.