Mart Ustav Jr will defenf his doctoral thesis titled „Molecular Studies of HPV-18 Genome Segregation and Stable Replication“ on 18 February 2016 at 9.15 at Nooruse 1-121.
Supervisor: prof. Mart Ustav (Tartu Ülikool), PhD Andres Männik (Icosagen AS)
Opponent: PhD Alison McBride, National Institute of Health, USA.
After the discovery of the link between papillomaviruses (HPV) and cervical cancer in the 1980’s, papillomavirus research has been directed towards the studies of the molecular mechanisms of induction of cervical cancer by the papillomaviruses. The preventive vaccine against HPV makes it is possible to avoid HPV infection, however a large number of people are still infected and HPV infection has not been effectively controlled yet. Thereby it is still important to continue to pursue HPV antivirals that could either block the viral DNA replication or stable maintenance of the viral genome in infected cells. In this thesis we describe immortalized human osteosarcoma cell line U2OS that is capable of supporting replication a number of different HPV subtypes. We describe further the transcriptional map of HPV-18 in U2OS cells and verify the relevancy of this system as the information obtained from these studies correlates with the previous findings of HPV-18 in primary keratinocytes. In the last part of this thesis we go in depth of the stable maintenance and segregation of HPV-18 DNA as we describe the cis-elements crucial for this function. We further validate this information in the context of the U2OS cells.
In conclusion we describe a cell line suitable for developing screening system for antivirals against HPV and we go in depth of describing crucial elements of HPV-18 DNA segregation.