Pentoxifylline Suppresses Transduction by HIV-1-Based VectorsSmith J.A. · Nunnari G. · Preuss M. · Pomerantz R.J. · Daniel R.
Division of Infectious Diseases, Center for Human Virology, Thomas Jefferson University, Philadelphia, Pa., USA
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Article / Publication Details
Pentoxifylline, a caffeine-related compound, was shown to suppress human immunodeficiency virus type 1 (HIV-1) replication. This effect is thought to be mediated by inhibition of tumor necrosis factor-alpha (TNFα)-mediated long-terminal repeat (LTR)-driven expression. We now demonstrate that pentoxifylline efficiently inhibits transduction by HIV-1-based vectors. This latter effect is independent of LTR-driven expression, and correlates with a reduced efficiency of the completion of the integration process in infected cells. Finally, the effect of pentoxifylline is dramatically reduced in cells expressing a dominant negative ATR protein, and in primary human cells that exhibit low level of ATR activity, suggesting that the effect of pentoxifylline on HIV-1 transduction and replication is at least partly mediated by suppression of the ATR kinase.
© 2007 S. Karger AG, Basel
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