title: Selective restriction of Nef-defective human immunodeficiency virus type 1 by a proteasome-dependent mechanism.
abstract: The Nef protein enhances human immunodeficiency virus type 1 (HIV-1) infectivity by facilitating an early postentry step in the virus life cycle. We report here that the addition of MG132 or lactacystin, each a specific inhibitor of cellular proteasome activity, preferentially enhances cellular permissiveness to infection by Nef-defective versus wild-type HIV-1. Pseudotyping by the glycoprotein of vesicular stomatitis virus rendered Nef-defective HIV-1 particles minimally responsive to the enhancing effects of proteasome inhibitors. These results suggest that Nef enhances the infectivity of HIV-1 particles by reducing their susceptibility to proteasomal degradation in target cells.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-2363, USA.
authors.forename: Mingli
authors.initials: M
authors.lastname: Qi
authors.forename: Christopher
authors.initials: C
authors.lastname: Aiken
mesh_terms: D003546:Cysteine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology; D015693:Gene Products, nef / Q000235:genetics* / Q000502:physiology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D046988:Proteasome Endopeptidase Complex; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex