Pentoxifylline, a caffeine-related compound, was shown tosuppress human immunodeficiency virus type 1 (HIV-1) replication.This effect is thought to be mediated by inhibitionof tumor necrosis factor-alpha (TNF )-mediated long-terminalrepeat (LTR)-driven expression. We now demonstratethat pentoxifylline efficiently inhibits transduction by HIV-1-based vectors. This latter effect is independent of LTR-drivenexpression, and correlates with a reduced efficiency of thecompletion of the integration process in infected cells. Finally,the effect of pentoxifylline is dramatically reduced incells expressing a dominant negative ATR protein, and in primaryhuman cells that exhibit low level of ATR activity, suggestingthat the effect of pentoxifylline on HIV-1 transductionand replication is at least partly mediated by suppressionof the ATR kinase.
Pentoxifylline suppresses transduction by HIV-1-based vectors
NUNNARI G;
2007-01-01
Abstract
Pentoxifylline, a caffeine-related compound, was shown tosuppress human immunodeficiency virus type 1 (HIV-1) replication.This effect is thought to be mediated by inhibitionof tumor necrosis factor-alpha (TNF )-mediated long-terminalrepeat (LTR)-driven expression. We now demonstratethat pentoxifylline efficiently inhibits transduction by HIV-1-based vectors. This latter effect is independent of LTR-drivenexpression, and correlates with a reduced efficiency of thecompletion of the integration process in infected cells. Finally,the effect of pentoxifylline is dramatically reduced incells expressing a dominant negative ATR protein, and in primaryhuman cells that exhibit low level of ATR activity, suggestingthat the effect of pentoxifylline on HIV-1 transductionand replication is at least partly mediated by suppressionof the ATR kinase.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
