title: Antiviral activity of the proteasome on incoming human immunodeficiency virus type 1.
abstract: Following cell surface receptor binding and membrane fusion, human immunodeficiency virus (HIV) virion cores are released in the cytoplasm. Incoming viral proteins represent potential targets for cytosolic proteases. We show that treatment of target cells with the proteasome inhibitors MG132 and lactacystin increased the efficiency of HIV infection. Proteasome inhibitors were active at the early steps of the viral cycle. Incoming p24Gag proteins accumulated in the cytosol, and larger amounts of proviral DNA were synthesized. In vitro, purified 20S proteasome degraded HIV virion components. Thus, degradation of incoming viral proteins by the proteasome represents an early intracellular defense against infection.
authors.affiliation: Laboratoire Rétrovirus et Transfert Génétique, URA CNRS 1157, Institut Pasteur, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Schwartz
authors.forename: V
authors.initials: V
authors.lastname: Maréchal
authors.forename: B
authors.initials: B
authors.lastname: Friguet
authors.forename: F
authors.initials: F
authors.lastname: Arenzana-Seisdedos
authors.forename: J M
authors.initials: JM
authors.lastname: Heard
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004279:DNA, Viral / Q000096:biosynthesis; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D007976:Leupeptins / Q000494:pharmacology / Q000633:toxicity; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004279:DNA, Viral; D015696:Gene Products, tat; D016655:HIV Core Protein p24; D007976:Leupeptins; D009097:Multienzyme Complexes; D054322:tat Gene Products, Human Immunodeficiency Virus; C067713:lactacystin; D001616:beta-Galactosidase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine