Characterization of a DNA Polymerase Mutant of Herpes Simplex Virus from a Severely Immunocompromised Patient Receiving Acyclovir

A series of herpes simplex virus isolates were recovered from a bone marrow transplant patient who received prolonged acyclovir therapy for indolent herpes simplex mouth and throat ulceration. Of 14 isolates received 10 were resistant o acyclovir and partially resistant to phosphonoacetic a id. Biochemical characteriza-tion revealed that resistance was due to an alteration in the virus DNA polymerase. DNA sequence analysis of the polymerase gene of a plaque-purified resistant virus isolate revealed a single nucleotide change when compared with the sequence of the gene of a plaque-purified sensitive isolate. This single base change resulted in a predicted amino acid substitution of Gly to Ser at residue number 841, a putative functional region of the polymerase