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Microbiology · Virology: HBV cccDNA persistence
Sample itemA man with chronic hepatitis B has had undetectable serum HBV DNA on tenofovir for five years. After he stops the drug, viraemia returns within months. Which viral feature mainly explains the relapse?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
B. Persistent nuclear cccDNA in hepatocytes
After entry, HBV converts its relaxed circular DNA into covalently closed circular DNA in the hepatocyte nucleus, where it acts as a stable minichromosome and template for viral RNAs. Polymerase inhibitors block reverse transcription but do not eliminate this reservoir, so stopping therapy lets replication resume.
Option by option
A. Latent provirus integrated in resting CD4 cells
Latent proviral DNA in CD4 cells is the reservoir of HIV, not HBV.
B. Persistent nuclear cccDNA in hepatocytes (correct)
Correct. Nucleoside analogues do not remove cccDNA, which re-seeds replication when drugs are stopped.
C. Universal selection of a resistant polymerase mutant
Resistance to tenofovir is rare and does not occur in every patient.
D. Latent virus in sensory ganglia neurons
Latency in sensory ganglia is a feature of herpes simplex and varicella-zoster viruses.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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