A 45-year-old renal transplant recipient on ganciclovir for CMV viremia shows rising viral load after 6 weeks of therapy. Genotypic testing reveals a mutation in the UL97 gene. What is the mechanism of ganciclovir resistance in this patient?

• A Mutation in DNA polymerase reducing drug binding
• B Decreased drug uptake into cells
• C Defective phosphorylation of ganciclovir ✓
• D Increased drug efflux from cells

Explanation

Ganciclovir requires phosphorylation by the viral UL97 phosphotransferase to become active. Mutations in UL97 prevent this initial phosphorylation step, leading to resistance. Mutations in UL54 (DNA polymerase) cause resistance at a later stage. Decreased uptake or increased efflux are not mechanisms of CMV ganciclovir resistance.

Reference: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 9th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.