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Journal of Virology, February 2005, p. 2058-2065, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2058-2065.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Caffeine Inhibits Human Immunodeficiency Virus Type 1 Transduction of Nondividing Cells

René Daniel,1* Elena Marusich,1 Elias Argyris,1 Richard Y. Zhao,2 Anna Marie Skalka,3 and Roger J. Pomerantz1

Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Thomas Jefferson University,1 Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania,3 Department of Pediatrics, Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois2

Received 9 July 2004/ Accepted 24 September 2004

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.

* Corresponding author. Mailing address: Thomas Jefferson University, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, JAH Suite 321, 1020 Locust St., Philadelphia, PA 19107. Phone: (215) 503-5725. Fax: (215) 923-1956. E-mail: Rene.Daniel{at}jefferson.edu.

Journal of Virology, February 2005, p. 2058-2065, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2058-2065.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ariumi, Y., Trono, D. (2006). Ataxia-Telangiectasia-Mutated (ATM) Protein Can Enhance Human Immunodeficiency Virus Type 1 Replication by Stimulating Rev Function. J. Virol. 80: 2445-2452 [Abstract] [Full Text]  


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