Herpes simplex acyclovir-resistant mutant in experimental keratouveitis

Area of Science:

• Virology
• Antiviral Drug Resistance
• Ophthalmology

Background:

• Acyclovir is a key antiviral medication for herpes simplex virus type 1 (HSV-1) infections.
• Drug-resistant HSV-1 mutants have emerged, posing a clinical challenge.
• Understanding the characteristics of resistant strains is crucial for effective treatment.

Purpose of the Study:

• To develop and characterize a laboratory-generated acyclovir-resistant HSV-1 mutant.
• To compare the virulence and latency of the resistant mutant with the wild-type strain.
• To evaluate the efficacy of alternative antiviral agents against the acyclovir-resistant HSV-1.

Main Methods:

• Development of an acyclovir-resistant HSV-1 mutant in the laboratory.
• Infection models using rabbit corneas to study keratitis.
• In vitro and in vivo assessments of viral sensitivity to different drugs.
• Measurement of thymidine kinase activity in the resistant mutant.

Main Results:

• The acyclovir-resistant HSV-1 mutant exhibited reduced virulence in keratitis compared to wild-type HSV-1.
• Ganglionic latency rates for the resistant mutant were comparable to the wild-type strain.
• In vitro and in vivo studies showed sensitivity of the resistant mutant to vidarabine and bromovinyldeoxyuridine.
• The resistant mutant's thymidine kinase activity was 69% of the wild-type strain.

Conclusions:

• Acyclovir-resistant HSV-1 mutants demonstrate altered virulence but retain significant latency potential.
• Vidarabine and bromovinyldeoxyuridine represent potential therapeutic options for acyclovir-resistant HSV-1 infections.
• Further research into alternative antivirals is warranted to combat drug-resistant HSV-1.