Immunoregulatory effects of HIV‐1 Nef protein

Abstract

During HIV infection, the perturbation of the adaptive and innate immune responses contributes to the progressive immunosuppression leading to an increased susceptibility to opportunistic infections and neoplastic diseases. Several impairments observed in HIV-infected patients include a gradual loss of CD4(+) T cells, CD8(+) T cell dysfunction, and a decreased number and function of natural killer (NK) cells. Moreover, a functional impairment and variation in the number of DC and B cells were observed during HIV infection. HIV-1 codes for proteins, including the accessory Nef proteins, that interacting with immune cells may contribute to AIDS pathogenesis. Here, we review the recent progress on the immunomodulatory effect of the accessory Nef protein and its role in the pathogenesis of HIV-1 infection. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc.

Dendritic Cell Response to HIV-1 Is Controlled by Differentiation Programs in the Cells and Strain-Specific Properties of the Virus

“…Endotoxin contamination of the recombinant proteins, on the other hand, was ruled out with the help of a THP-1-XBlue bioassay system (detection limit 0.05 EU/ml). The HIV-1 protein Nef has been described to modulate DC functions acting in a bystander manner or, alternatively, within the infected cells (20). Similar to gp120, preincubation of DCs obtained from dense or sparse cultures with recombinant Nef resulted in a profound inhibition of the ability of the cells to produce IL-12 in response to a later LPS activation (Figure 5B).…”

HIV-1 Nef Transfer and Intracellular Signalling in Uninfected Cells

“…In addition it has been described to inhibit p53-mediated apoptosis binding the tumor suppressor (Greenway et al, 2002). As a consequence of Nef ability to bind multiple targets it is plausible that depending on Nef subcellular localization and the availability of particular subset of targets (for example Hck versus Lck tyrosine kinase), certain Nef effects dominate over others in a time-and cell type-dependent manner thus differing in infected monocyte/macrophages versus T lymphocytes, DC, astrocytes or microglial cells (see Quaranta et al, 2009 for the different regulatory effects of Nef in immune cells). In macrophages, that are important target of HIV infection and reservoir of the virus, Nef expression induces the release of a set of paracrine factors including a marked increase of CCL2/MIP-1 and CCL4/MIP-1 chemokines.…”

HIV-1 Nef Signaling in Intestinal Mucosa Epithelium Suggests the Existence of an Active Inter-kingdom Crosstalk Mediated by Exosomes

“…Depending on its intracellular localization, Nef may exert multiple effects such as interfering with cellular signal transduction pathways or modulating the cell surface expression of many membrane-associated proteins in infected cells (Greenway et al, 2003; Quaranta et al, 2009). In particular, Nef can affect the T-cell signaling pathways and increase the infectivity of new virus particles released from the cell (Fujii et al, 1996; Aiken, 2015).…”

“…Nef can be internalized from extracellular environment and accumulated in B cells in the germinal centers of infected lymphoid follicles. Nef can render B cells less responsive to CD4 + T activation, inhibiting the switching to IgG, IgA, and IgE (Quaranta et al, 2009) and blocking the CD40 ligand. Moreover, Nef increases infectivity of produced HIV-1 virions, by preventing the incorporation of two antiviral cellular proteins, SERINC3 and SERINC5 (Rosa et al, 2015; Usami et al, 2015).…”