Peroxisome-Human Papillomavirus Infection Nexus and Implications

Human Papillomavirus (HPV) causes 5% of all cancers and 300,000 annual deaths, disproportionately impacting global health due to gender and socioeconomic inequalities. Despite this burden, critical gaps remain in our understanding of its infectious life cycle, particularly how it exploits host cellular organelles for persistent infection. PerFection aims to bridge this critical gap by investigating how HPV manipulates peroxisomes — vital organelles recognised for their multifaceted roles in cellular homeostasis and innate immunity — to promote viral persistence and drive oncogenesis. PerFection involves three core actions, integrating cutting-edge multidisciplinary methodologies: 1. generate comprehensive HPV-peroxisome interaction map using advanced bioinformatics, molecular and structural biology techniques to pinpoint key connections; 2. functionally investigate how these interactions alter peroxisome metabolism, redox homeostasis and biogenesis by employing omics and cellular imaging approaches; 3. determine how interfering with these mapped interactions affects HPV's overall manipulation of peroxisomes and thus its ability to establish or maintain infection using 3D cell models. This structured approach will reveal precise molecular mechanisms by which the virus manipulates peroxisomes, providing a deeper understanding of fundamental HPV biology. This novel knowledge will identify entirely new host-targeted vulnerabilities, which could pave the way for urgently needed alternative antiviral strategies and host-directed therapies. Ultimately, PerFection aims to contribute to a reduction in HPV-related illness and associated deaths by providing solutions beyond current vaccine access or extensive screening infrastructure. It will also advance the fields of cell biology, virology, and infectious disease research by offering a blueprint for investigating other underappreciated organelles and fostering future innovation in diagnostics and therapies.