Cytomegalovirus protein kinase pUL97 (pUL97 kinase)

Cytomegalovirus protein kinase pUL97 is a serine/threonine protein kinase encoded by the human cytomegalovirus (HCMV) and is essential for efficient viral replication. pUL97 acts as a viral cyclin-dependent kinase (vCDK) ortholog, sharing functional and structural features with host CDKs and interacting with human cyclins (B1, T1, H) to regulate its diverse functions. It phosphorylates both viral and host proteins, including those critical for viral nuclear egress, immune evasion, and the function of various host transcription complexes. pUL97 mediates the activating monophosphorylation of several nucleoside analog antiviral drugs (such as ganciclovir), and is itself a validated target for specific kinase inhibitors, notably maribavir, in antiviral therapy. Resistance to pUL97-targeting drugs is a clinical concern, typically due to point mutations in the UL97 gene. The protein exists in several isoforms and is mainly localized in the nucleus. Its inhibition results in a dramatic reduction in viral replication and impaired viral nuclear egress, underscoring its importance as a therapeutic target in HCMV infection management.

Other names

Human cytomegalovirus protein kinase pUL97UL97 kinaseHCMV pUL97viral cyclin-dependent kinase (vCDK/pUL97)

Kinase inhibitors: Inhibit pUL97 catalytic activity, impairing viral replication and nuclear egress (e.g., maribavir). Nucleoside analog prodrugs: Require pUL97-mediated monophosphorylation for activation (e.g., ganciclovir, valganciclovir).