Ubiquitin is part of the retrovirus budding machinery.
Retroviruses contain relatively large amounts of ubiquitin, but the significance of this finding has been unknown. Here, we show that drugs that are known to reduce the level of free ubiquitin in the cell dramatically reduced the release of Rous sarcoma virus, an avian retrovirus. This effect was suppressed by overexpressing ubiquitin and also by directly fusing ubiquitin to the C terminus of Gag, the viral protein that directs budding and particle release. The block to budding was found to be at the plasma membrane, and electron microscopy revealed that the reduced level of ubiquitin results in a failure of mature virus particles to separate from each other and from the plasma membrane during budding. These data indicate that ubiquitin is actually part of the budding machinery.
Patnaik
A
A
Department of Microbiology and Immunology and Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, 500 University Drive, P.O. Box 850, Hershey, PA 17033, USA.
Chau
V
V
Wills
J W
JW
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001358:Avian Sarcoma Viruses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure / Q000821:virology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004705:Endocytosis; D015683:Gene Products, gag / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D011784:Quail; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D015683:Gene Products, gag; D007976:Leupeptins; D009097:Multienzyme Complexes; D009842:Oligopeptides; D011480:Protease Inhibitors; D011993:Recombinant Fusion Proteins; D014452:Ubiquitins; C067713:lactacystin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000111:Acetylcysteine; C078846:epoxomicin