In HIV-1, drug resistance emerges rapidly. Which specific property of its reverse transcriptase most directly explains the high mutation rate that fuels resistance to antiretroviral drugs?

Introduction / Context:
HIV-1 evolves rapidly in patients, often selecting variants that resist antiretroviral drugs. Central to this adaptability is the fidelity of reverse transcriptase (RT), the enzyme that copies viral RNA into DNA. This item probes which molecular property of RT most directly accounts for the high mutation rate driving resistance.

Given Data / Assumptions:

• HIV-1 RT synthesizes viral DNA from an RNA template.
• Mutations arise during genome replication.
• Drug resistance correlates with replication error rates.

Concept / Approach:
DNA polymerases with a 3'→5' exonuclease (proofreading) can remove misincorporated nucleotides, lowering error rates. HIV-1 RT lacks this proofreading function, so mismatches persist, producing a high mutation frequency that accelerates resistance selection under drug pressure.

Step-by-Step Solution:

Verification / Alternative check:
Comparative biochemistry shows polymerases with proofreading (e.g., many replicative DNA polymerases) have far lower error rates than HIV-1 RT, aligning with observed rapid viral evolution.

Why Other Options Are Wrong:

• AZT cost does not determine mutation rate; it is a socioeconomic factor, not an enzymatic property.
• RNase H degrades RNA in RNA–DNA hybrids; it does not set base-substitution fidelity.
• Low affinity for correct dNTPs would reduce processivity, not specifically increase substitution errors as observed.
• RT does not use ribonucleotides to synthesize DNA; it uses deoxyribonucleotides.

Common Pitfalls:
Confusing processivity or RNase H function with proofreading; assuming resistance arises mainly from recombination rather than frequent point mutations produced by error-prone synthesis.

Final Answer:
It lacks a 3'→5' proofreading exonuclease activity