Dendritic keratitis caused by an acyclovir-resistant herpes simplex virus with frameshift mutation

Area of Science:

• Ophthalmology
• Virology
• Genetics

Background:

• Herpes simplex virus (HSV) keratitis is a common ocular infection.
• Long-term or inconsistent use of topical antivirals like acyclovir can lead to drug resistance.
• Steroid use, such as fluorometholone, may also influence HSV recurrence and resistance patterns.

Observation:

• A 70-year-old male presented with dendritic keratitis.
• The causative HSV strain demonstrated resistance to acyclovir, with a 50% inhibitory concentration of 13.75 microg/mL.
• Viral thymidine kinase sequencing revealed a frameshift mutation in a 7-guanine homopolymer region.

Findings:

• The isolated HSV strain was significantly resistant to acyclovir but susceptible to trifluorothymidine (50% inhibitory concentration of 0.28 microg/mL).
• A specific frameshift mutation in the viral thymidine kinase gene was identified as the likely cause of acyclovir resistance.
• Topical trifluorothymidine treatment led to complete resolution of the epithelial lesion within two weeks.

Implications:

• This case underscores the potential for acyclovir resistance in HSV keratitis, particularly with non-adherent treatment regimens.
• Genetic analysis of viral thymidine kinase is crucial for diagnosing resistance mechanisms.
• Trifluorothymidine represents a viable alternative treatment for acyclovir-resistant HSV keratitis.