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Caffeine inhibits human immunodeficiency virus type 1 transduction of nondividing cells

René Daniel1, Elena Marusich, Elias Argyris

  • 1Thomas Jefferson University, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, JAH Suite 321, 1020 Locust St., Philadelphia, PA 19107, USA. Rene.Daniel@jefferson.edu

Journal of Virology
|February 1, 2005
PubMed

Insights

Caffeine inhibits human immunodeficiency virus type 1 (HIV-1) transduction in both dividing and nondividing cells. This effect is partly mediated by the ataxia telangiectasia-mutated and Rad3-related (ATR) kinase pathway, independent of cell cycle checkpoints.

Area of Science:

  • Molecular biology
  • Virology
  • Cell biology

Background:

  • Caffeine inhibits DNA repair and DNA damage-activated checkpoints.
  • Caffeine has been shown to inhibit retroviral transduction of dividing cells, likely by blocking postintegration repair.
  • The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase is a potential cellular target for caffeine's effects.

Purpose of the Study:

  • To investigate the effect of caffeine on human immunodeficiency virus type 1 (HIV-1) transduction in nondividing cells.
  • To determine if the ATR kinase pathway mediates caffeine's inhibition of HIV-1 transduction.
  • To assess the role of cell cycle checkpoints in caffeine's effect on HIV-1 transduction.

Main Methods:

  • Treatment of growth-arrested, terminally differentiated human neurons, and macrophages with caffeine.
  • Transduction assays using HIV-1 vectors, including a Vpr-deficient vector.
  • Analysis of HIV-1 transduction in cells expressing a dominant-negative ATR protein (ATRkd).

Main Results:

  • Caffeine reduced HIV-1 transduction in growth-arrested and terminally differentiated cells.
  • The inhibitory effect of caffeine was observed with a Vpr-lacking HIV-1 vector.
  • HIV-1 transduction was reduced in ATRkd-expressing cells and showed relative resistance to caffeine.

Conclusions:

  • Caffeine's inhibition of HIV-1 transduction in nondividing cells is partly mediated by the ATR pathway.
  • The effect of caffeine on HIV-1 transduction is independent of its inhibition of cell cycle checkpoints.

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