Abstract
Objectives: Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV) types 6 and 11. However, the cellular and molecular mechanisms underlying its pathogenesis remain to be elucidated. Recently, the conditional reprogramming (CR) method, which reprograms epithelial cells to an undifferentiated stem cell state, has been shown to be effective for studying RRP. Here, we investigated the relationship between viral and host gene expression in CR cells and explored the molecular pathogenesis of RRP. Methods: We evaluated the passage capacity and growth rate of CR cells from fresh RRP tissues and adjacent normal tissues from patients with RRP. Furthermore, we performed RNA-seq analysis of CR cells across multiple passages to characterize the gene expression profiles associated with RRP. Results: RRP-derived CR cells exhibited greater passage capacity and proliferation rates than adjacent normal tissue-derived CR cells. HPV6 gene was expressed in all RRP-derived CR cells and its expression decreased with each passage. We identified three categories of genes correlated with HPV6: inflammatory genes (e.g., CTSS, CFB), oncogenic genes (e.g., CEACAM5, CEACAM6), and glycosylation-related genes (e.g., ST6GALNAC1, FUT2). Conclusion: HPV6-induced gene expression signature in infected epithelial cells may play a role in RRP pathogenesis. Further molecular investigations are necessary to determine whether controlling these genes and related factors can control the progression of RRP. Level of evidence: N/A.