Clustered localization of oligomeric Nef protein of human immunodeficiency virus type 1 on the cell surface

Abstract

One report has shown that Nef molecules expressed by Abstract We studied human immunodeficieney virus type 1 (HIV-1) Nef protein biochemically and histologically. HIV-1 bacterial and eukaryotic systems form oligomers [11], but Nef, derived from baculosystem and from cells infected with there is no information about the oligomerization of Nef in HIV-I, formed homomeric monomers, dimers, trimers, and HIV-l-infected T cells. To clarify the mechanism of Nef-defurther polymers. These oligomers were non-covalently assopendent cell killing, we studied the biochemical and histologiciated. In cells infected with HIV-1, Nefmolecules were clustered cal properties of Nef. In this report we show that the Nef at the cell surface as well as cytoplasm. Our previous results have molecules form oligomers and cluster on the surface of indicated that the Nef on the surface of cells infected with HIV-1 HIV-1-infected CD4+ cells. is cytotoxic against uninfected CD4+ T cells. Thus, it is very likely that the HIV-l-medlated cytotoxic reaction is due, at least in part, to the clustered localization of oligomeric Nef on the cell 2. Materials and methods surface. Cells and antibodies

HIV-1 envelope induces activation of caspase-3 and cleavage of focal adhesion kinase in primary human CD4+T cells

“…Marked impairment in the functional capability of CD4 ϩ T lymphocytes as well as in other cellular immune responses additionally characterizes HIV disease (48,49). These deficiencies in immune function are associated with the replication of HIV and͞or the production of HIV-encoded gene products (50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Although no single viral protein is likely to be the sole effector of immune dysfunction, the viral envelope is believed to contribute significantly to immune system impairment (reviewed in refs.…”

Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development

“…Nef oligomers have been reported by several groups, 43,44 but their importance in Nef activities has not been elucidated yet. In the Nef oligomers, Asp123 is interacting with the conserved di-arginine motif Arg105Arg106 of another protomer.…”

The activity of Nef on HIV-1 infectivity

“…Nef is myristoylated, which contributes to its association with membranes, together with a stretch of basic aminoacids close to the N-terminus (Bentham et al, 2006). Indeed, a significant fraction of Nef is observed in association with the plasma membrane and perinuclear membrane complexes (Kohleisen et al, 1992; Fujii et al, 1996; Greenberg et al, 1997). Myristoylation may also contribute to prevent Nef from multimerizing (Breuer et al, 2006).…”