The HIV-Nef protein has been implicated in generating high viral loads and T cell activation. Transgenic (tg) mice with constitutive T cell-specific Nef expression show a dramatic reduction in T cell number and highly increased T cell turnover. Previous studies in Nef tg mice attributed this T cell activation to a direct effect of Nef at the cellular level. Given the strongly reduced peripheral...

OBJECTIVE To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects. DESIGN We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir ...

The Nef protein of the type 1 human immunodeficiency virus (HIV-1) plays a key although poorly understood role in accelerating the progression of clinical disease in vivo. Nef exerts several biological effects in vitro, including enhancement of virion infectivity, downregulation of CD4 and major histocompatibility complex class I receptor expression, and modulation of various intracellular sign...

Lipid rafts are membrane microdomains that are functionally distinct from other membrane regions. We have shown that 10% of human immunodeficiency virus type 1 (HIV-1) Nef expressed in SupT1 cells is present in lipid rafts and that this represents virtually all of the membrane-associated Nef. To determine whether raft targeting, rather than simply membrane localization, has functional significa...

Nef is a 27 - 34 kD myristoylated protein unique to primate lentiviruses. A functional Nef gene is important for development of high viremia and simian AIDS in SIV infected rhesus macaques (1). In a transgenic mouse model expression of Nef protein alone when expressed under a CD4-promoter is sufficient to cause an AIDS like disease (2). A critical role for Nef in development of AIDS in humans i...

In collapsing focal segmental glomerulosclerosis (FSGS) of HIV-associated nephropathy (HIVAN), podocytes exhibit a high proliferation rate and loss of differentiation markers. We have found previously that the nef gene of HIV-1 is responsible for these changes. Here, we investigated the signaling pathways induced by Nef and its role in the pathogenesis of HIVAN. Using conditionally immortalized...

The human immunodeficiency virus type 1 (HIV-1) nef gene encodes a 27-kDa protein that plays a crucial role during AIDS pathogenesis, but its exact functional mechanism has not been fully elucidated and remains controversial. The present study illuminated the in vivo functions of Nef using Drosophila, in which genetic analyses can be conveniently conducted. Using Drosophila transgenic lines for...

Considerable controversy and uncertainty have surrounded the biological function of the Human Immunodeficiency Virus (HIV)-1 nef gene product. Initial studies suggested that this early, nonstructural viral protein functioned as a negative regulatory factor; thus, it was proposed to play a role in establishing or maintaining viral latency. In contrast, studies in Simian Immunodeficiency Virus (S...

The nef genes of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) encode a 27- to 34-kDa myristoylated protein which induces downregulation of CD4 surface levels and enhances virus infectivity. In adult macaques, Nef has been implicated in pathogenesis and disease progression. Both HIV-1 SF2 Nef and SIVmac239 Nef have been shown to associate with a cellular se...

Human immunodeficiency virus 1 (HIV-1) downregulates cell surface expression of HLA-A and HLA-B but not HLA-C or HLA-E to ultimately escape immune defences. Here, it is shown that cell surface expression of the non-classical HLA-G1 is also downregulated by HIV-1, by using co-transfection experiments and infection with cell-free HIV-1 of HLA-G1-expressing U87 glioma cells or macrophages in prima...