A neutropenic post-transplant patient develops CMV pneumonitis. The drug of choice for CMV disease is ganciclovir. Which enzyme of CMV phosphorylates ganciclovir to its active monophosphate form?
- A Thymidine kinase (same as HSV)
- B UL97 protein kinase (CMV phosphotransferase) ✓
- C Host cell adenylate kinase
- D CMV DNA polymerase (UL54)
Explanation
CMV encodes the UL97 protein kinase (phosphotransferase), which phosphorylates ganciclovir to ganciclovir monophosphate; host cell kinases then complete the phosphorylation to the active triphosphate form that inhibits viral DNA polymerase. This is distinct from Herpes simplex virus, which uses thymidine kinase (TK) for the initial phosphorylation step. CMV resistance to ganciclovir most commonly arises from mutations in UL97, and mutations in the viral DNA polymerase (UL54) confer higher-level resistance. Acyclovir is a poor CMV antiviral because UL97 phosphorylates acyclovir very inefficiently.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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