Acquired resistance to acyclovir: laboratory phenomenon or clinical problem?

Area of Science:

• Virology
• Antimicrobial Resistance
• Molecular Biology

Background:

• Herpes simplex virus (HSV) is a common human pathogen.
• Nucleoside analogue inhibitors, such as acyclovir, are key antiviral treatments for HSV infections.
• In vitro studies show HSV can rapidly develop resistance to these drugs.

Purpose of the Study:

• To investigate the mechanisms of HSV resistance to nucleoside analogue inhibitors.
• To identify the genetic loci responsible for antiviral drug resistance in HSV.
• To discuss the implications of drug resistance for future clinical applications.

Main Methods:

• Herpes simplex virus cultures were exposed to nucleoside analogue inhibitors.
• Mutant strains exhibiting resistance were isolated and characterized.
• Genetic analysis focused on thymidine kinase (TK) and DNA polymerase genes.

Main Results:

• The most frequent in vitro resistant mutants were thymidine kinase-negative (TK-).
• Some resistant strains demonstrated low levels of thymidine kinase enzyme activity.
• Resistance mechanisms involve alterations in viral TK or DNA polymerase.

Conclusions:

• HSV readily develops resistance to acyclovir and related drugs in vitro.
• Mutations in the TK gene are the primary cause of resistance.
• Understanding these resistance mechanisms is crucial for managing HSV infections as antiviral use expands.