Related Experiment Video
Updated: Aug 11, 2026
Recurrent Herpetic Stromal Keratitis in Mice, a Model for Studying Human HSK
Published on: December 18, 2012
Development of clinical resistance to acyclovir in herpes simplex virus-infected mice receiving oral therapy
Abstract:
Mice inoculated in the ear pinna with herpes simplex virus were treated effectively by including 1 mg of acyclovir per ml in the drinking water. During a 5-day course of treatment the development of resistance was not readily apparent. However, when a suboptimal therapeutic dose was used and virus was repeatedly inoculated into further mice undergoing therapy, the infection became completely refractory to treatment by passage 4. Some of the viruses isolated exhibited reduced ability to induce thymidine kinase, and this appeared to account at least in part for the development of resistance. However, the viruses isolated from the tissues of such mice comprised complex mixtures of strains with widely differing in vitro susceptibilities to acyclovir. The properties of these virus yields gave an indication of the likely nature of resistance to nucleoside analogs in humans and suggested some difficulties which may be encountered when clinical specimens are analyzed.
Insights
Acyclovir effectively treated herpes simplex virus in mice, but resistance developed with repeated exposure. This resistance was linked to reduced thymidine kinase activity and complex viral mixtures, offering insights into nucleoside analog resistance in humans.
Area of Science:
- Virology
- Pharmacology
- Antiviral Drug Resistance
Background:
- Herpes simplex virus (HSV) infections are common, and antiviral treatments like acyclovir are crucial.
- Understanding the mechanisms of antiviral resistance is vital for effective treatment strategies.
Purpose of the Study:
- To investigate the development of acyclovir resistance in herpes simplex virus in a murine model.
- To explore the virological and biochemical basis of resistance to nucleoside analogs.
Main Methods:
- Mice with HSV ear pinna infections were treated with acyclovir in drinking water.
- Viral resistance was assessed through repeated passages and in vitro susceptibility testing.
- Thymidine kinase activity of isolated viruses was measured.
Main Results:
- Acyclovir treatment was initially effective, but resistance emerged after serial passages with suboptimal dosing.
- Developed resistance was associated with reduced viral thymidine kinase activity.
- Viral isolates comprised complex mixtures of strains with varying acyclovir susceptibilities.
Conclusions:
- Suboptimal acyclovir therapy can lead to the emergence of resistant HSV strains.
- Resistance mechanisms involve alterations in viral enzymes like thymidine kinase.
- Analysis of clinical specimens may be complicated by the presence of mixed resistant and susceptible viral strains.
