Human cytomegalovirus protein kinase pUL97 (pUL97)

Human cytomegalovirus protein kinase pUL97 is a multifunctional serine/threonine kinase encoded by the UL97 gene of Human Cytomegalovirus (HCMV) [2, 5]. It is characterized as a viral ortholog of cellular cyclin-dependent kinases (vCDK) due to its ability to interact with host cyclins and phosphorylate similar substrates, such as the retinoblastoma (Rb) protein and nuclear lamins [7, 10, 16]. The enzyme plays a pivotal role at multiple stages of the viral replication cycle, including the regulation of viral gene expression, DNA synthesis, and the nuclear egress of newly formed capsids [3, 4, 8]. pUL97 is a clinically significant therapeutic target; the antiviral drug maribavir acts as a competitive inhibitor of its kinase activity, effectively blocking viral production [1, 6, 9]. Furthermore, pUL97 is essential for the pharmacological activation of the prodrug ganciclovir, as it performs the initial monophosphorylation step required for its antiviral effect [4, 11, 13]. Mutations within the UL97 gene are the primary mechanism of viral resistance to both ganciclovir and maribavir, making it a critical focus for monitoring treatment efficacy in immunocompromised and transplant patients [8, 9].

Other names

HCMV pUL97UL97 kinaseViral cyclin-dependent kinase orthologvCDKGanciclovir kinase

Maribavir acts as a competitive inhibitor of the pUL97 kinase at the ATP-binding site, preventing the phosphorylation of viral and cellular substrates necessary for viral replication, encapsidation, and nuclear egress [1, 6, 8]. Additionally, pUL97 serves as the activating enzyme for ganciclovir and its analogs by performing the initial monophosphorylation step required for their antiviral activity [4, 11].