Stochastic Modeling of the Co-Regulation between Early and E8 Promoters in Human Papillomavirus.

Abstract

High risk HPV can induce cervical and oropharyngeal cancerous Iesions. The initial phase of the infection is characterized by a fine regulation of the viral DNA replication, in order to maintain 10-100 DNA copies per cell. Such regulation is primarily controlled by El and E2 proteins produced by the early promoter. The recently discovered E8 promoter is capable to co-regulate the early one in order to maintain a low and constant viral DNA copy number.The aim of this study is to develop a novel stochastic mathematical model of the co-regulation between the E8 and the early promoter, with the main purpose to rigorously show the E8 promoter capability to finely regulate the HPV transcripts which control the DNA replication in the first stages of the infection.The model, condensing the biological knowledge present in literature, describes the interaction between the two promoters and shows how the E8 co-regulation is capable to reject the stochastic noise of E2 gene expression to a higher extent than the early promoter negative auto-feedback. This proves the capability of the E8 promoter to finely control the HPV genomes copy number.