The Nef protein of primate lentiviruses

The Nef protein of primate lentiviruses acts as an important virulence fact or in vivo both in monkeys and in humans. Among a human cohort of long-term non-progressors, several Nef defective HIV1 viruses have been isolated, in dicating that Nef may accelerate HIV progression and disease in humans. Add itionally, a Nef-deleted SIV virus has low titres in rhesus monkeys and the animals develop AIDS at a much slower rate. In vitro, Nef can exert at lea st three kinds of effects: it downregulates CD4 and MHC class I, it stimula tes virion infectivity and it alters signal transduction pathways. To accom plish this, Nef interacts with a series of cellular partners including CD4, components of the adaptor complexes AP-1 and AP-2, and several protein kin ases, Nef often functioning as a connector between targets and effecters. T he high degree of understanding of at least some aspects of Nef action, as well as the importance of this viral gene product for disease induction, id entify Nef as a valuable target for the development of novel antiviral ther apies. Moreover, the possibility of developing vaccines using attenuated vi ruses with deletions in nef and other crucial genes raises the possibility that the AIDS epidemic might one day be restrained. Copyright (C) 1999 John Wiley & Sons, Ltd.