SpringerImages - Schematic presentation of selected Nef functions and interactions in infected T cells. Nef interacts with HLA molecules, CD4, CD28, CXCR4, and CD3 to reduce their surface expression on infected CD4+ T cells, thereby reducing CTL lysis, suppressing cell migration, facilitating virus release and modulating signal transduction by the immunological synapse. Furthermore, Nef interacts with a variety of cellular kinases and other factors to modulate downstream signaling events. HIV-1 Nef promotes the activation of transcription factors, such as NF-AT, NF-κB, and AP-1, to induce the efficient transcription of the viral LTR promoter and of various cellular genes, e.g., those encoding for inflammatory cytokines, activation markers and death receptors. Furthermore, Nef down-modulates CD4 to promote virus release and to prevent superinfection and enhances virus replication and virion infectivity to directly promote virus spread. Please note that the presentation is preliminary and shows only a small proportion of all reported effects of Nef and that not all primate lentiviral Nefs perform all indicated functions

Caption

Fig 1

Schematic presentation of selected Nef functions and interactions in infected T cells. Nef interacts with HLA molecules, CD4, CD28, CXCR4, and CD3 to reduce their surface expression on infected CD4+ T cells, thereby reducing CTL lysis, suppressing cell migration, facilitating virus release and modulating signal transduction by the immunological synapse. Furthermore, Nef interacts with a variety of cellular kinases and other factors to modulate downstream signaling events. HIV-1 Nef promotes the activation of transcription factors, such as NF-AT, NF-κB, and AP-1, to induce the efficient transcription of the viral LTR promoter and of various cellular genes, e.g., those encoding for inflammatory cytokines, activation markers and death receptors. Furthermore, Nef down-modulates CD4 to promote virus release and to prevent superinfection and enhances virus replication and virion infectivity to directly promote virus spread. Please note that the presentation is preliminary and shows only a small proportion of all reported effects of Nef and that not all primate lentiviral Nefs perform all indicated functions

Extracts from the Article What's this?

2004) (Fig. 1).

Many of the receptors modulated by Nef are involved in the formation of the immunological synapse (Fig. 1), which requires the interaction of the TCR-CD3 complex on T cells with the Ag/MHC-II complex expressed by APCs and of co-stimulatory and adhesion molecules on both cells.

Besides performing multiple functions that facilitate viral immune evasion, Nef also modulates the activation status of the infected T cells and enhances the infectivity of progeny virions to promote viral replication (Fig. 1).

Thus, HIV-1 Nef may partly uncouple T cell activation from the “normal” antigen-dependent interaction with APCs to increase virus production (Fig. 1).

Since HIV-1 requires T cell activation for efficient replication, Nef’s subversion of T cell signaling pathways increases the transcriptional activity of the viral LTR promoter to promote efficient viral replication (Fig. 1)..

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