title: Comparison of human cytomegalovirus (HCMV) protease sequences among laboratory strains and seven clinical isolates.
abstract: The nucleotide sequence of the human cytomegalovirus (HCMV) protease gene from two laboratory strains and seven clinical isolates, both ganciclovir-sensitive and -resistant, was examined to determine the genetic variability of the HCMV protease catalytic domain and to identify changes that may alter the efficacy of designed protease inhibitors. The Towne strain varied from AD169 at 12 nucleotides and led to one amino acid change at position 12 (Ala to Thr). The clinical isolates had amino acid substitutions relative to the laboratory strains, with a Ser to Pro change at position 8, a His to Tyr change at position 44 and s Gly to Ser change at position 47. None of these changes occurred in any of the conserved domains of the protease, nor do they appear necessary to confer ganciclovir resistance in the isolates. These findings suggest that no changes exist in the protease of the clinical isolates examined that may diminish the effectiveness of a drug targeting the HCMV protease. 1977 Elsevier Science B.V. All rights reserved.
authors.affiliation: Pharmacology and Molecular Biology Groups, Agouron Pharmaceuticals, CA 92121, USA.
authors.forename: T K
authors.initials: TK
authors.lastname: Huffaker
authors.forename: S
authors.initials: S
authors.lastname: Binford
authors.forename: A K
authors.initials: AK
authors.lastname: Patick
authors.forename: C
authors.initials: C
authors.lastname: Pinko
authors.forename: C C
authors.initials: CC
authors.lastname: Kan
authors.forename: L S
authors.initials: LS
authors.lastname: Zalman
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D003587:Cytomegalovirus / Q000201:enzymology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000821:virology; D010450:Endopeptidases / Q000235:genetics*; D005814:Genes, Viral; D006801:Humans; D009154:Mutation; D012697:Serine Endopeptidases; D013045:Species Specificity; D014764:Viral Proteins / Q000235:genetics
chemical_list: D014764:Viral Proteins; D010450:Endopeptidases; C087225:human cytomegalovirus protease UL80; D012697:Serine Endopeptidases; C071910:assemblin