HIV reverse transcriptase — Identify the function it explicitly lacks (consider template use, directionality, and primer requirement)

Introduction:
HIV reverse transcriptase is a hallmark enzyme of retroviruses that converts viral RNA into DNA. This question tests detailed conceptual understanding of which activities the enzyme has and, critically, which activity it does not possess, because that absence explains HIV’s high mutation rate.

Given Data / Assumptions:

• The enzyme uses viral RNA as a template to synthesize DNA.
• Reverse transcriptase works with a primer (typically a host tRNA).
• Polymerization occurs in the 5' to 3' direction like other DNA polymerases.
• Proofreading activity would mean 3' to 5' exonuclease activity that removes misincorporated nucleotides.

Concept / Approach:
Reverse transcriptase has two main catalytic functions: RNA dependent DNA polymerase and RNase H (degrades RNA in RNA–DNA hybrids). It lacks the canonical 3' to 5' exonuclease proofreading found in many high-fidelity DNA polymerases. This deficiency leads to frequent replication errors and rapid viral evolution.

Step-by-Step Solution:

Verification / Alternative check:
Error rates measured for reverse transcriptase are much higher than for replicative DNA polymerases, consistent with no 3' to 5' proofreading. Antiretroviral drugs like nucleoside reverse transcriptase inhibitors exploit the enzyme’s active site chemistry and primer dependence but do not confer proofreading.

Why Other Options Are Wrong:

• Uses RNA as a template: correct; fundamental to reverse transcription.
• Has 5' to 3' polymerase activity: correct; all DNA synthesis proceeds 5' to 3'.
• Requires a primer: correct; the enzyme cannot initiate de novo synthesis.
• Can synthesize cDNA from RNA: restates its core function.

Common Pitfalls:
Assuming all polymerases proofread. Many specialized polymerases, especially reverse transcriptases, sacrifice fidelity for function, accelerating viral diversity.

Final Answer:
Has 3' to 5' exonuclease proofreading activity.