Complex mechanisms of human immunodeficiency virus type-1 (HIV-1) brain pathogenesis suggest the contribution of individual HIV-1 gene products. Among them, the Nef protein has been reported to harbor a major determinant of pathogenicity in AIDS-like disease. The goal of the present study was to determine whether Nef protein expressed in vivo by primary macrophages could induce a brain toxicity...

Let (M, E) be a generalized polarized manifold, i.e., a pair of an n-dimensional smooth projective variety and an ample vector bundle E of rank r on M . Let τ be the nef value of a polarized manifold (M, det E), i.e., the minimum of the set of real numbers t such that KM + tdet E is nef; we have τr ≤ n+ 1 by Mori’s theory. In this paper we classify the pairs (M, E) in the following two cases: (...

1. Root Space Decompositions 2 2. Weights 5 3. Weyl Group 8 4. Irreducible Representations 11 5. Basic Concepts of Vector Bundles 13 6. Line Bundles 17 7. Curvature 20 7.1. Curvature of tangent bundles 22 7.2. Curvature of line bundles 24 7.3. Levi curvature 25 8. Ampleness Formulas 27 8.1. Ampleness of irreducible bundles 28 8.2. Ampleness of tangent bundles 29 9. Chern Classes 32 9.1. Chern c...

We are using site-directed mutagenesis of single viral genes to identify and analyze the genetic determinants of human and simian immunodeficiency virus pathogenicity. In a first approach, we have constructed a series of simian immunodeficiency virus SIVmac nef mutants by partial deletion and insertions in the nef gene, as this gene is a candidate gene for the establishment and maintenance of l...

Linearised fluctuating hydrodynamics describes effectively the concentration non-equilibrium fluctuations (NEF) arising during a diffusion process driven by a small concentration gradient. However, fluctuations in the presence of large gradients are not yet fully understood. Here we study the giant concentration NEF arising when a dense aqueous colloidal suspension is allowed to diffuse into an...

Alterations of T-cell receptor signaling by human immunodeficiency virus type 1 (HIV-1) Nef involve its association with a highly active subpopulation of p21-activated kinase 2 (PAK2) within a dynamic signalosome assembled in detergent-insoluble membrane microdomains. Nef-PAK2 complexes contain the GTPases Rac and Cdc42 as well as a factor providing guanine nucleotide exchange factor (GEF) acti...

Increasing evidence indicates that the expression of the human immunodeficiency virus-1 (HIV-1) Nef protein significantly influences the activation state of the host cell. Here we report that Nef specifically activates STAT3 in primary human monocyte-derived macrophages (MDM). This was demonstrated by both single-cycle infection experiments driven by Vesicular Stomatitis virus glycoprotein (VSV...

The HIV Nef protein downregulates the cell-surface expression of the HIV receptor glycoprotein CD4, but the significance of this event has remained obscure. Recent data suggest that Nef reduces cell-surface CD4 to promote the efficient spread of the virus.

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...

BACKGROUND The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins ...