A renal transplant recipient on valacyclovir prophylaxis develops progressive mucocutaneous herpes simplex lesions despite therapy. Phenotypic testing shows the isolate grows normally in cell culture but is not inhibited by acyclovir. The most likely molecular defect is:

• A Mutation in viral DNA polymerase reducing drug binding
• B Deletion of the glycoprotein D gene
• C Overexpression of the viral UL42 processivity factor
• D Loss of functional viral thymidine kinase ✓

Explanation

Acyclovir is a prodrug that must be phosphorylated initially by the viral thymidine kinase to acyclovir monophosphate; cellular kinases then generate the active triphosphate. Most clinical acyclovir resistance in HSV arises from loss or alteration of the viral thymidine kinase gene, leaving the drug unactivated. Distractor A is a real but much less common resistance mechanism seen mainly with foscarnib-cross-resistant isolates. Such resistant strains respond to foscarnet, which bypasses thymidine kinase entirely.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.