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J Virol. 2005 Feb;79(4):2058-65.

Caffeine inhibits human immunodeficiency virus type 1 transduction of nondividing cells.

Author information

  • 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

Abstract

Caffeine is an efficient inhibitor of DNA repair and DNA damage-activated checkpoints. We have shown recently that caffeine inhibits retroviral transduction of dividing cells, most likely by blocking postintegration repair. This effect may be mediated at least in part by a cellular target of caffeine, the ataxia telangiectasia-mutated and Rad3-related (ATR) kinase. In this study, we present evidence that caffeine also inhibits efficient transduction of nondividing cells. We observed reduced transduction in caffeine-treated growth-arrested cells as well as caffeine-treated terminally differentiated human neurons and macrophages. Furthermore, this deficiency was observed with a human immunodeficiency virus type 1 (HIV-1) vector lacking Vpr, indicating that the effect is independent of the presence of this viral protein in the infecting virion. Finally, we show that HIV-1 transduction of nocodazole-arrested cells is reduced in cells that express an ATR dominant-negative protein (kinase-dead ATR [ATRkd]) and that the residual transduction of ATRkd-expressing cells is relatively resistant to caffeine. Taken together, these data suggest that the effect(s) of caffeine on HIV-1 transduction is mediated at least partly by the inhibition of the ATR pathway but is not dependent on the caffeine-mediated inhibition of cell cycle checkpoints.

PMID:
15681408
[PubMed - indexed for MEDLINE]
PMCID:
PMC546572
Free PMC Article

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