Spontaneous reactivation of thymidine kinase-deficient, acyclovir-resistant type-2 herpes simplex virus: masked heterogeneity or reversion?

The Effects and Pharmacokinetics of Acyclovir in Neonates

    Acyclovir (9-[2-hydroxyethoxymethyl] guanine) is an acyclic nucleoside analogue of guanosine which is a potent and selective antiviral agent. Acycloviris converted to the monophosphate by thymidine kinase the virus-specific form of this enzyme and is subsequently converted to the triphosphate by the host cell kinase. Acyclovir triphosphate inhibits viral DNA-polymerase terminating the chain...

Pathogenesis of acyclovir-resistant herpes simplex type 2 isolates in animal models of genital herpes: models for antiviral evaluations.

Our understanding of the pathogenesis of acyclovir (ACV)-resistant herpes simplex virus (HSV) is limited, especially with regard to reactivation and recurrent disease. To further explore the pathogenesis of ACV-resistant HSV-2 viruses, we used the guinea pig model of genital HSV-2 infection to evaluate several ACV-resistant isolates of both thymidine kinase (Tk)-altered and Tk-deficient phenoty...

Low-level expression and reversion both contribute to reactivation of herpes simplex virus drug-resistant mutants with mutations on homopolymeric sequences in thymidine kinase.

Many acyclovir-resistant herpes simplex virus isolates from patients contain insertions or deletions in homopolymeric sequences in the thymidine kinase (TK) gene (tk). Viruses that have one (G8) or two (G9) base insertions in a run of seven G's (G string) synthesize low levels of active TK (TK-low phenotype), evidently via ribosomal frameshifting. These levels of TK can suffice to permit reacti...

Restriction Enzyme Analysis of Thymidine Kinase Gene in Four Iranian Isolates of Herpes Simplex Virus Type 1

Biological and biochemical characterization of clinical isolates of herpes simplex virus type 2 resistant to acyclovir.

A series of clinical isolates of herpes simplex virus type 2 were taken from a patient with chronic lymphocytic leukemia. Acyclovir (ACV) susceptibility assays revealed that some isolates were resistant to ACV and cross-resistant to ganciclovir but not to phosphonoacetic acid. The nature of the resistance was examined further. A number of cloned variants were generated, and thymidine kinase and...