title: Contributions of HIV-1 Nef to immune dysregulation in HIV-infected patients: a therapeutic target?
abstract: BACKGROUND
  HIV accessory protein Nef is a factor responsible for many of the viral pathogenic effects. Progression to AIDS is dramatically delayed and in some well-documented cases completely abolished on infection with naturally occurring HIV strains lacking intact nef sequences in their genomes. The topic of this review is the contribution of Nef to the immune pathology as a possible target in HIV-infected patients.
  
  
  METHODS
  An overview of known Nef functions accounting for its role in pathogenesis is presented, emphasizing interactions with dendritic cells and macrophages, and Nef-induced exosome secretion, all involved in immune dysregulation during the course of HIV infection. Current approaches to Nef inhibition by different classes of compounds are reviewed.
  
  
  CONCLUSIONS
  Blocking Nef for therapeutic purposes is a challenging endeavor mainly due to intrinsic properties of this HIV accessory protein. Nef has multiple interfaces to interact with host proteins and lacks a catalytic domain. Potential benefits arising from the development of successful inhibitors could however prove beneficial for reducing gradual deterioration of immune system in chronically infected patients in absence of functional cure.
authors: Department of Clinical Chemistry, Microbiology and Immunology of Ghent University , Gent , Belgium +32 93323658 ; +32 93323659 ; bruno.verhasselt@ugent.be.
authors: Wojciech
authors: W
authors: Witkowski
authors: Bruno
authors: B
authors: Verhasselt
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D015693:Gene Products, nef / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D015693:Gene Products, nef