CHARACTERIZATION OF THE HUMAN CYTOMEGALOVIRUS UL97 GENE-PRODUCT AS A VIRION-ASSOCIATED PROTEIN-KINASE

The cellular localization and virion association of the human cytomega lovirus (HCMV) UL97 protein were studied. UL97 protein demonstrated ea rly nuclear localization followed by late perinuclear accumulation. It was found to be a structural virion constituent detected in all three enveloped forms of extracellular viral particles and shown to be phos phorylated by the virion-associated protein kinase. UL97 protein immun oprecipitated from virions and from infected cells demonstrated protei n kinase activity manifested by autophosphorylation. This activity was reduced in the presence of a ganciclovir-resistance mutation at resid ue 460, implicated in nucleotide binding. A mutant virus, from which t he proposed UL97 kinase catalytic domain had been deleted, could not b e propagated in the absence of a helper wild-type virus. The character ization of UL97 protein as a virion-associated protein kinase which ap pears essential for viral replication, provides further insight into H CMV replication and could identify a potential novel target for antivi ral therapy.