Human cytomegalovirus protein kinase UL97 (also referred to as pUL97 or UL97 kinase) (UL97)

The human cytomegalovirus (HCMV) UL97 protein kinase is a serine/threonine viral enzyme that functions as a virally-encoded cyclin-dependent kinase-like protein (v-Cdk).[1][2] UL97 is essential for efficient HCMV replication through multiple critical functions: it phosphorylates the cellular retinoblastoma tumor suppressor to stimulate cell cycle progression and support viral DNA synthesis, phosphorylates nuclear lamins to facilitate capsid egress from the nucleus, prevents aggregation of viral structural proteins, and enhances viral gene expression through phosphorylation of RNA polymerase II.[1][2][3] The kinase is also uniquely targeted by the antiviral drug ganciclovir, which UL97 phosphorylates to its active form that subsequently inhibits viral DNA polymerase.[1] UL97 represents a validated therapeutic target for HCMV infection, particularly in immunocompromised patients, with multiple antiviral strategies including direct kinase inhibitors (such as maribavir) and nucleoside analogs (such as ganciclovir) in clinical use or development.[1][4] The main therapeutic challenge involves the emergence of resistance mutations in the UL97 gene that can compromise drug efficacy.

Other names

pUL97UL97 kinaseSerine/threonine protein kinase UL97Viral-encoded cyclin-dependent kinase-like kinase (v-Cdk)Conserved herpesvirus protein kinase (CHPK) from human cytomegalovirus

Kinase inhibition: Direct inhibition of UL97 enzymatic activity (e.g., maribavir) prevents phosphorylation of viral and cellular substrates; Substrate phosphorylation: Ganciclovir is phosphorylated by UL97 to become an active nucleotide analog that inhibits viral DNA polymerase; Disruption of viral replication: Inhibiting UL97 activity impairs viral DNA synthesis, virion morphogenesis, and nuclear egress