The human immunodeficiency virus type 1 virulence protein Nef interacts with the endosomal sorting machinery via a leucine-based motif. Similar sequences within the cytoplasmic domains of cellular transmembrane proteins bind to the adaptor protein (AP) complexes of coated vesicles to modulate protein traffic, but the molecular basis of the interactions between these motifs and the heterotetrame...

UNLABELLED The role of the accessory viral Nef protein as a multifunctional manipulator of the host cell that is required for effective replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) in vivo is well established. It is unknown, however, whether Nef manipulates all or just specific subsets of CD4(+) T cells, which are the main targets of virus infection ...

Using heteronuclear NMR spectroscopy, we demonstrate that a 13-residue peptide (MS-QIKRLLSEKKT) from the cytoplasmic tail of CD4 binds to Nef protein. This part of CD4 is critical for downregulation of CD4 by HIV-1 Nef [Aiken et al. (1994) Cell 76, 853-864]. We show that a control peptide without the central dileucine does not bind to Nef. The dependence of Nef 1H and 15N amide chemical shifts ...

The Nef protein of primate immunodeficiency viruses plays an important role in the pathogenesis of acquired immunodeficiency syndrome (AIDS) [1] [2]. The interaction of Nef with the Nef-associated kinase (NAK) is one of the most conserved properties of different human and simian immunodeficiency virus (HIV and SIV) Nef alleles. The role of NAK association is currently not known but it has been ...

Nef, a approximately 200 residue multifunctional regulatory protein of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), interacts with components of host cell signal transduction and clathrin-dependent protein sorting pathways. The downregulation of surface CD4 molecules and major histocompatibility complex (MHC) class I antigens by Nef is believed to be important in ...

We have recently identified the Nef-associated serine-threonine kinase (NAK) as the p21-activated kinase 2 (PAK2). Here we have taken advantage of the possibility to manipulate the functional properties of NAK by transfecting PAK2 cDNA or its mutant derivatives in order to further characterize the Nef-NAK complex. To exclude the possibility that some Nef variants might interact with PAK1 instea...

The accessory protein negative factor (Nef) from human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) is required for optimal viral infectivity and the progression to acquired immunodeficiency syndrome (AIDS). Nef interacts with the endocytic machinery, resulting in the down-regulation of cluster of differentiation antigen 4 (CD4) and major histocompatibility complex class...

Lentiviral Nef increases viral replication in vivo, plays a direct role in pathogenesis, and increases viral particle infectivity. We now find that HIV Nef also increases the activation of T cells, a cellular state required for optimal viral replication. This enhancement is stimulant-dependent. As defined by IL-2 generation, activation of T cells stimulated with classical mitogens [phorbol 12-m...

In this issue of Cell, Schindler et al. (2006) show that the Nef protein from nonpathogenic strains of simian immunodeficiency virus (SIV) induces the downregulation of host T cell receptor/CD3, whereas Nef from human immunodeficiency virus (HIV-1) does not. This loss of function in the Nef of HIV-1 may partly explain the pathogenicity of this virus.

BACKGROUND Plants may represent excellent alternatives to classical heterologous protein expression systems, especially for the production of biopharmaceuticals and vaccine components. Modern vaccines are becoming increasingly complex, with the incorporation of multiple antigens. Approaches towards developing an HIV vaccine appear to confirm this, with a combination of candidate antigens. Among...