Rapid degradation of CD4 in cells expressing human immunodeficiency virus type 1 Env and Vpu is blocked by proteasome inhibitors.
Human immunodeficiency virus (HIV) type 1 encodes three genes, Vpu, Env and Nef, that decrease cellular CD4. Vpu and Env act cooperatively to accelerate degradation of CD4 in the endoplasmic reticulum. Here we report that Vpu/Env-induced CD4 degradation is inhibited by lactacystin, a specific inhibitor of the proteasome, and by other proteasome inhibitors, but not by non-proteasome protease inhibitors. We also note that Vpu has amino acid sequence homology with a segment of IkappaB known to be involved in proteasome-mediated degradation, suggesting that HIV-1 could have transduced cellular sequences to enhance down-regulation of CD4.
Fujita
K
K
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Omura
S
S
Silver
J
J
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000595:Amino Acid Sequence; D020126:Brefeldin A; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism*; D003517:Cyclopentanes / Q000494:pharmacology; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D015686:Gene Products, env / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D015398:Signal Transduction / Q000502:physiology*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000086082:Viroporin Proteins
D000111:Acetylcysteine; D020126:Brefeldin A; D015704:CD4 Antigens; D003517:Cyclopentanes; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D015686:Gene Products, env; D054298:Human Immunodeficiency Virus Proteins; D007976:Leupeptins; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D054334:Viral Regulatory and Accessory Proteins; C089487:acetyl-leucinyl-leucinyl-methional; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C067713:lactacystin