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Updated: May 27, 2026

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells
13:07

Determining 3'-Termini and Sequences of Nascent Single-Stranded Viral DNA Molecules during HIV-1 Reverse Transcription in Infected Cells

Published on: January 30, 2019

RING domain mutations uncouple TRIM5α restriction of HIV-1 from inhibition of reverse transcription and acceleration

Amanda Roa1, Fumiaki Hayashi, Yang Yang

  • 1Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, New York, USA.

Journal of Virology
|November 25, 2011
PubMed

Insights

Rhesus TRIM5α (TRIM5α(rh)) restricts HIV-1 by accelerating viral uncoating, preventing reverse transcription. This mechanism blocks infection before integration, offering new insights into viral restriction.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Rhesus TRIM5α (TRIM5α(rh)) is a key antiviral protein restricting HIV-1 postentry.
  • TRIM5α(rh) function is linked to reduced viral capsid levels during infection.
  • The precise mechanism of TRIM5α(rh) in blocking reverse transcription remains incompletely understood.

Purpose of the Study:

  • To genetically dissect how TRIM5α influences HIV-1 reverse transcription.
  • To investigate the role of TRIM5α(rh) RING domain mutations in viral restriction.
  • To correlate TRIM5α's effect on capsid stability with its ability to block viral replication.

Main Methods:

  • Generated and analyzed TRIM5α(rh) RING domain mutants.
  • Assessed HIV-1 restriction, reverse transcription, and integration.
  • Utilized nuclear magnetic resonance (NMR) to evaluate protein folding.
  • Measured pelletable viral capsid levels and TRIM5α degradation.

Main Results:

  • TRIM5α(rh) RING mutants restricted HIV-1 post-reverse transcription, forming 2-LTR circles.
  • Mutations impairing reverse transcription also reduced capsid destabilization.
  • TRIM5α(rh) RING variants prevented TRIM5α degradation after HIV-1 entry.
  • Accelerated uncoating correlated with the block of reverse transcription.

Conclusions:

  • TRIM5α(rh) blocks HIV-1 reverse transcription by inducing premature viral uncoating.
  • The TRIM5α(rh) RING domain is critical for this uncoating-dependent restriction.
  • TRIM5α's ability to accelerate uncoating is a key mechanism for inhibiting HIV-1 replication.

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