A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells

摘要: HUMAN cytomegalovirus (HCMV) is a major pathogen in immunosuppressed individuals, including patients with acquired immune deficiency syndrome. The nucleoside analogue ganciclovir (9-(l,3-dihydroxy-2-propoxymethyl)-guanine) one of the few drugs available to treat HCMV infections, but resistant virus growing problem clinic1 and there critical need for new drugs. study ganciclovir-resistant mutants has indicated that selective action depends largely on virus-controlled phosphorylation HCMV-infected cells2–5. enzyme(s) responsible have not been identified. Here we report gene UL97, whose predicted product shares regions homology protein kinases, guanylyl cyclase bacterial phosphotransferases6–8, controls cells. A four-amino-acid deletion UL97 conserved region, which cyclic AMP-dependent kinase participates substrate recognition9, causes impaired phosphorylation. implications these results antiviral drug development resistance are discussed.