On 03 September at 12:15 Elina Lototskaja-Perepelenko will defend her doctoral thesis “Protein kinases as regulators of human papillomavirus replication proteins” for obtaining the degree of Doctor of Philosophy (Biomedical Engineering)
Supervisiors:
Associate Professor Alla Piirsoo, University of Tartu
Senior Specialist of Cell and Tissue Technology Marko Piirsoo, University of Tartu
Opponent:
Research Director Françoise Bachelerie, Université Paris-Saclay (France)
Summary: Human papillomaviruses (HPVs) are widespread viruses that infect the skin and mucous membranes. Some HPV types are well known because of their role in anogenital cancers, whereas much less is understood about the types that infect the skin. These skin-associated HPVs may contribute to non-melanoma skin cancer, particularly in people with weakened immune systems, in combination with ultraviolet radiation.
HPVs rely heavily on the cells they infect to complete their life cycle. This thesis examined how cellular protein kinases - enzymes that regulate activity, stability, and subcellular localisation of proteins - control HPV replication through the viral proteins E1 and E2. These proteins are essential for copying and maintaining the viral genome.
The results of my thesis reveal that the same cellular signalling pathways can influence different HPV types in distinct ways. In skin-infecting HPV, the addition of a phosphate group to a single amino acid of the E2 protein was required for efficient viral genome replication. The kinase CK2 supported the replication of several mucosal and skin-associated HPV types by stabilising the E1 protein and promoting its retention in the cell nucleus, where viral DNA replication occurs. By contrast, PKA had opposite effects on different HPV groups: it enhanced the replication of mucosal HPVs by increasing E1 and E2 levels, but suppressed skin-associated HPV by promoting rapid degradation of E2.
Together, these findings demonstrate that even closely related HPVs can respond differently to the same cellular regulatory mechanisms. This diversity is important when considering antiviral strategies that target cellular kinases, because a treatment that inhibits one HPV type may have a different or even opposite effect on another.
Defence can be followed in Zoom: Doctoral Defence (meeting ID: 953 058 8152, passcode: kaitsmine).
