Cell cycle arrest in G2/M promotes early steps of infection by human immunodeficiency virus

Bettina Groschel1, Frederic Bushman

  • 1University of Pennsylvania School of Medicine, Department of Microbiology, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA.

Journal of Virology
|April 14, 2005
PubMed

Insights

Four small molecules that induce cell cycle arrest enhance human immunodeficiency virus (HIV) transduction. G2/M cell cycle arrest significantly boosts early HIV replication steps in various cell types.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Human immunodeficiency virus (HIV) infection relies on efficient cellular transduction.
  • Understanding factors that modulate HIV replication is crucial for developing antiviral strategies and gene therapy vectors.
  • Cell cycle regulation plays a significant role in viral replication dynamics.

Purpose of the Study:

  • To identify small molecules that enhance HIV transduction.
  • To elucidate the mechanism by which these molecules boost HIV replication, focusing on cell cycle modulation.
  • To assess the potential of cell cycle arrest for improving HIV-based vector efficiency.

Main Methods:

  • Treatment of various cell lines (293T, HeLa) and primary cells (IMR90) with etoposide, camptothecin, taxol, and aphidicolin.
  • Induction of cell cycle arrest at G2/M and G1 phases using these compounds and serum starvation/contact inhibition.
  • Analysis of early HIV replication events, including reverse transcription, 2-long terminal repeat circle formation, and proviral integration.
  • Investigation of the combined effects of cell cycle inhibitors and the proteasome inhibitor MG132.

Main Results:

  • Four small molecules (etoposide, camptothecin, taxol, aphidicolin) were found to boost HIV transduction.
  • Cell cycle arrest at G2/M by these compounds significantly increased early HIV replication steps in both transformed and primary cells.
  • High concentrations of aphidicolin causing G1 arrest also boosted transduction, but less effectively than G2/M arrest.
  • MG132, a proteasome inhibitor, may also enhance transduction by inducing G2/M arrest.

Conclusions:

  • Cell cycle arrest, particularly at the G2/M phase, is a key factor that enhances early stages of HIV infection.
  • These findings provide insights into the mechanism of HIV replication and suggest strategies for improving transduction efficiency using HIV-based vectors.

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