Protein Kinase CK2 and Epstein–Barr Virus, 2023, Mathias Montenarh et al

Abstract
Protein kinase CK2 is a pleiotropic protein kinase, which phosphorylates a number of cellular and viral proteins. Thereby, this kinase is implicated in the regulation of cellular signaling, controlling of cell proliferation, apoptosis, angiogenesis, immune response, migration and invasion.

In general, viruses use host signaling mechanisms for the replication of their genome as well as for cell transformation leading to cancer. Therefore, it is not surprising that CK2 also plays a role in controlling viral infection and the generation of cancer cells. Epstein–Barr virus (EBV) lytically infects epithelial cells of the oropharynx and B cells. These latently infected B cells subsequently become resting memory B cells when passing the germinal center. Importantly, EBV is responsible for the generation of tumors such as Burkitt’s lymphoma. EBV was one of the first human viruses, which was connected to CK2 in the early nineties of the last century.

The present review shows that protein kinase CK2 phosphorylates EBV encoded proteins as well as cellular proteins, which are implicated in the lytic and persistent infection and in EBV-induced neoplastic transformation. EBV-encoded and CK2-phosphorylated proteins together with CK2-phosphorylated cellular signaling proteins have the potential to provide efficient virus replication and cell transformation. Since there are powerful inhibitors known for CK2 kinase activity, CK2 might become an attractive target for the inhibition of EBV replication and cell transformation.

Conclusions
In the present review, we demonstrated that protein kinase CK2 is strongly implicated in the regulation of EBV viral replication, in persistent infection and in cell transformation leading to cancer. These different functions are achieved through the phosphorylation of virally encoded proteins as well as through the phosphorylation of cellular proteins, which are regulators of cellular signaling pathways such as the NF-κB, PIP3/Akt, JAK/STAT, and Wnt/Dishevelled/β-catenin signaling pathways.

CK2 and EBV act on the same cellular signaling pathways. It remains to be elucidated whether and how EBV hijacks CK2 to influence these different signaling pathways for neoplastic transformation. The binding of CK2 subunits to viral and cellular proteins might reflect an enzyme–substrate interaction.

Alternatively, the interactions might target CK2 to other substrates. Since a great number of different CK2 kinase inhibitors are now known, some of which have already been used to inhibit signaling pathways, these inhibitors are promising tools for the inhibition of virus replication as well as of virally induced cancers. Very recently, CK2 was found to play a role in SARS-CoV-2 infections [45]. The knowledge of the role of CK2 in EBV infection might also help to find new strategies to fight COVID-19.

https://www.mdpi.com/2227-9059/11/2/358