COMPARISON OF HUMAN CYTOMEGALOVIRUS (HCMV) PROTEASE SEQUENCES AMONG LABORATORY STRAINS AND 7 CLINICAL ISOLATES

The nucleotide sequence of the human cytomegalovirus (HCMV) protease g ene from two laboratory strains and seven clinical isolates, both ganc iclovir-sensitive and -resistant, was examined to determine the geneti c variability of the HCMV protease catalytic domain and to identify ch anges 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 am ino 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 a Gly to Ser change at position 47. None of these changes occurred in an y of the conserved domains of the protease, nor do they appear necessa ry to confer ganciclovir resistance in the isolates. These findings su ggest that no changes exist in the protease of the clinical isolates e xamined that may diminish the effectiveness of a drug targeting the HC MV protease. (C) 1997 Elsevier Science B.V.