title: [Regulation of human papillomavirus (HPV) genome replication in the viral life cycle and its association with the viral persistence and cancer development].
abstract: High-risk human papillomavirus (HR-HPV) infections account for more than 5% of all cancers (11% in women) such as cervical cancer worldwide. HPVs infect to basal cells of the stratified squamous epithelium and establish persistent infection within the basal compartment. HR-HPV infections can persist more than a decade, leading to development of cancers. The life cycle of HPVs is tightly associated with the differentiation processes of the stratified squamous epithelium; the replication of the viral genome and the expression of the viral genes are strictly regulated depending on differentiation of the host keratinocytes. The viral genome is transiently amplified immediately following infection and then maintained at constant copy numbers in the basal cells. In terminally differentiating keratinocytes, the viral genome is drastically amplified. However, molecular mechanisms underlying switching these three stages of viral genome replication in the viral life cycle are poorly understood. Recently, it has become evident that DNA damage response pathways are involved in the regulation of HPV genome replication. In this review, we would like to introduce recent findings describing the associations of DNA damage response with HPV genome replication.
authors.affiliation: National Cancer Center Research Institute, Division of Virology.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nakahara
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
mesh_terms: D052685:Alphapapillomavirus / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004265:DNA Helicases / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology / Q000821:virology; D005260:Female; D018628:Gene Dosage; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D005814:Genes, Viral / Q000235:genetics; D016679:Genome, Viral / Q000235:genetics*; D006801:Humans; D008018:Life Cycle Stages / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D004265:DNA Helicases