Replication of some HPV types is modulated by cAMP-dependent protein kinase activity

Date

2020

Journal Title

Journal ISSN

Volume Title

Publisher

Tartu Ülikool

Abstract

Human papillomaviruses (HPVs) are dsDNA viruses infecting basal keratinocytes of the cutaneous and mucosal epithelia. Some HPVs are tumorigenic; therefore, studies of the viral life cycle may help to develop novel treatment strategies. Protein kinases are important enzymes that regulate numerous cellular processes. HPV E1 and E2 regulatory proteins have several putative consensus sites for many kinases including cAMP-dependent protein kinase (PKA). The main focus of this thesis was to generate the constructs encoding the FLAG-tagged PKA catalytic subunit α (PKACα) and its two catalytically deficient mutants, and to investigate the influence of the over-expressed PKA proteins on replication of HPV types 5, 11, and 18 in U2OS cells. Additionally, PKA activator IBMX and inhibitor H89 were used to demonstrate the impact of the endogenous PKA catalytic activity on the replication efficiency of the HPV5 genome. Finally, the mechanism of the PKA-mediated stimulation of the HPV18 replication was studied.

Description

Keywords

human papillomavirus (HPV), replication, transcription, protein kinase A (PKA)

Citation