A 25-year-old immunocompromised patient develops recurrent genital HSV-2 infections. Which specific antiviral resistance mechanism leads to acyclovir treatment failure in HSV infections?

• A Mutation in DNA polymerase causing reduced incorporation of acyclovir triphosphate
• B Upregulation of viral efflux pumps
• C Mutation in viral capsid protein preventing drug entry
• D Deletion or point mutation in thymidine kinase (TK) gene leading to deficient phosphorylation of acyclovir ✓

Explanation

Acyclovir resistance in HSV most commonly (>95% of cases) results from mutations in the thymidine kinase (TK) gene. Acyclovir must first be monophosphorylated by viral TK before cellular kinases complete the process to the active triphosphate form. TK-deficient or TK-altered HSV strains cannot phosphorylate acyclovir. DNA polymerase mutations are a less common second mechanism. Treatment of acyclovir-resistant HSV uses foscarnet (directly inhibits viral DNA polymerase without requiring TK activation) or cidofovir.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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