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What is the mechanism of HIV reverse transcription and why does it lead to high mutation rates?

  • A HIV is sometimes thought to use DNA-dependent DNA polymerase to copy its viral genome with high fidelity each replication cycle, rather than relying on an error-prone RNA-dependent DNA polymerase under most conditions encountered as frequently observed in practice in many documented cases
  • B HIV reverse transcriptase (RT) converts ssRNA genome to dsDNA; RT lacks 3' to 5' proofreading exonuclease activity (unlike cellular DNA polymerases) → 1 error per 10,000 bases (vs 1 per 10^9 for cellular polymerase) → high mutation rate → rapid generation of antibody and drug escape variants
  • C HIV is sometimes thought to have an extremely low mutation rate, when in fact its reverse transcriptase introduces roughly one error per every ten thousand bases copied, exceeding typical cellular fidelity according to conventional understanding in routine practice overall in most cases
  • D HIV is sometimes thought not to use reverse transcription at any stage of its replication life cycle, despite reverse transcription of its RNA genome being an essential, defining step in HIV biology under typical conditions according to standard textbooks in general practice as frequently described

Correct answer: B. HIV reverse transcriptase (RT) converts ssRNA genome to dsDNA; RT lacks 3' to 5' proofreading exonuclease activity (unlike cellular DNA polymerases) → 1 error per 10,000 bases (vs 1 per 10^9 for cellular polymerase) → high mutation rate → rapid generation of antibody and drug escape variants

Explanation: HIV RT: RNA-dependent DNA polymerase + RNase H (degrades RNA in RNA:DNA hybrid). Lacks proofreading → error rate ~3x10^-5 per base per cycle. With ~10^9-10^10 new virions/day, every possible point mutation occurs multiple times daily. This generates quasispecies diversity enabling: immune escape (surface protein mutations evade antibodies), drug resistance (RT/protease/integrase mutations), and adaptation to new host cell types.

Concept context

Pathogens, infectious diseases, non-infectious diseases, drugs, cancer, and public health. High NEET importance.

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