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Rapid degradation of CD4 in cells expressing human immunodeficiency virus type 1 Env and Vpu is blocked by proteasome inhibitors.


J Gen Virol. 1997 Mar;78 ( Pt 3):619-25. Unique Identifier : AIDSLINE

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.

*Acetylcysteine/ANALOGS & DERIVATIVES *Antigens, CD4/METABOLISM *Cysteine Proteinase Inhibitors/PHARMACOLOGY *Gene Products, env/METABOLISM *Gene Products, vpu/METABOLISM *HIV-1/METABOLISM *Leupeptins/PHARMACOLOGY *Signal Transduction/PHYSIOLOGY


Information in this article was accurate in June 30, 1997. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.