Pentoxifylline suppresses transduction by HIV-1-based vectors.
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 (TNFalpha)-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.
Smith
Johanna A
JA
Division of Infectious Diseases, Center for Human Virology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Nunnari
Giuseppe
G
Preuss
Mirjam
M
Pomerantz
Roger J
RJ
Daniel
René
R
D000998:Antiviral Agents / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D002460:Cell Line; D005822:Genetic Vectors / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D010431:Pentoxifylline / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D014161:Transduction, Genetic; D016662:Virus Integration / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D018797:Cell Cycle Proteins; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D010431:Pentoxifylline