Genomic instability of the host cell induced by the human papillomavirus replication machinery.
Development of invasive cervical cancer upon infection by 'high-risk' human papillomavirus (HPV) in humans is a stepwise process in which some of the initially episomal 'high-risk' type of HPVs (HR-HPVs) integrate randomly into the host cell genome. We show that HPV replication proteins E1 and E2 are capable of inducing overamplification of the genomic locus where HPV origin has been integrated. Clonal analysis of the cells in which the replication from integrated HPV origin was induced showed excision, rearrangement and de novo integration of the HPV containing and flanking cellular sequences. These data suggest that papillomavirus replication machinery is capable of inducing genomic changes of the host cell that may facilitate the formation of the HPV-dependent cancer cell.
Kadaja
Meelis
M
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Sumerina
Alina
A
Verst
Tatjana
T
Ojarand
Mari
M
Ustav
Ene
E
Ustav
Mart
M
D052685:Alphapapillomavirus / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics / Q000502:physiology*; D042822:Genomic Instability / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D008954:Models, Biological; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics*; D014779:Virus Replication / Q000502:physiology*
D009856:Oncogene Proteins, Viral