PATTERNS OF RESISTANCE AND SENSITIVITY TO ANTIVIRAL COMPOUNDS OF DRUG-RESISTANT STRAINS OF HUMAN CYTOMEGALOVIRUS SELECTED IN-VITRO

Drug-resistant human cytomegalovirus (HCMV) strains were selected in h uman embryonic lung (MEL) fibroblasts under pressure of the (S)-3-hydr oxy-2-phosphonylmethoxypropyl (HPMP) derivatives of cytosine (HPMPC) a nd adenine (HPMPA), the 2-phosphonylmethoxyethyl (PME) derivative of 2 ,6-diaminopurine (PMEDAP), ganciclovir (GCV), acyclovir (ACV), and fos carnet (PFA). Drug susceptibility profiles of the different drug-resis tant (i.e., GCV(r), HPMPC(r), HPMPA(r), PFA(r), ACV(r), and PMEDAP(r)) strains were determined in MEL cells. A considerable degree of cross- resistance against GCV, HPMPC, and HPMPA occurred with the GCV(r), HPM PC(r), and HPMPA(r) strains. No changes in susceptibility to 9-(2-phos phonylmethoxyethyl)adenine (PMEA), PMEDAP, ACV, or PFA were detected f or the HPMPC(r), HPMPA(r), and GCV(r) strains when compared to the wil d-type virus. On the other hand, a significant degree of cross-resista nce was noted with the PMEDAP(r), PFA(r), and ACV(r) strains against P MEA, PMEDAP, PFA, and ACV. No differences in susceptibility to HPMPC, HPMPA and GCV were observed for the ACV(r), PFA(r), and PMEDAP(r) stra ins relative to the wild type. The drug susceptibility profiles of the different resistant strains point to a common mechanism of HCMV resis tance to PFA and the PME derivatives that is different from the mechan ism of HCMV resistance to the HPMP derivatives.