Differential Susceptibility of Several Drug-Resistant Strains of Herpes Simplex Virus Type 2 to Various Antiviral Compounds

Drug-resistant herpes simplex virus type 2 (HSV-2) strains were obtained under the selective pressure of acyclovir, ganciclovir, brivudin, foscamet, 2-phosphonyl-methoxyethyl (PME) derivatives of adenine (PMEA) and 2,6-diaminopurine (PMEDAP), and 3-hydroxy-2-phosphonylmethoxypropyl (HPMP) derivatives of adenine (HPMPA) and cytosine (HPMPC; cidofovir). A significant degree of cross-resistance between HPMPC and HPMPA on the one hand, and between PMEA, PMEDAP and foscarnet on the other, was noted, suggesting a different mode of interaction of the PME and HPMP derivatives at the DNA polymerase level. The results described here with HSV-2 agree with the published results for HSV-1 and human cytomegalovirus.