Binding of HIV-1 Nef to a novel thioesterase enzyme correlates with Nef-mediated CD4 down-regulation. NLM AIDSLINE Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Click here to return to AIDSLINE main menu
DonateNow
Print this Article


Binding of HIV-1 Nef to a novel thioesterase enzyme correlates with Nef-mediated CD4 down-regulation.

J Biol Chem. 1997 May 23;272(21):13779-85. Unique Identifier : AIDSLINE MED/97298085
Liu LX; Margottin F; Le Gall S; Schwartz O; Selig L; Benarous R; Benichou S; Institut Cochin de Genetique Moleculaire, INSERM U332, Universite; Paris V, 24 Rue du Faubourg Saint-Jacques, 75014 Paris, France.

Abstract: Nef is a 27-kDa myristoylated protein conserved in primate lentiviruses. In vivo, simian immunodeficiency virus Nef is required in macaques to produce a high viral load and full pathological effects. Nef has at least three major effects in vitro, induction of CD4 down-regulation, alteration of T cell activation pathways, and enhancement of viral infectivity. We have used the yeast two-hybrid system to identify cellular proteins that interact with HIV-1Lai Nef and could mediate Nef function. A human cDNA was isolated that encodes a new type of thioesterase, an enzyme that cleaves thioester bonds. This novel thioesterase is unlike the animal types I and II thioesterases previously cloned but is homologous to the Escherichia coli thioesterase II. Nef and this thioesterase interact in vitro and are co-immunoprecipitated by anti-Nef antibodies in CEM cells expressing Nef. Nef alleles from human immunodeficiency virus-1 HIV-1) isolates unable to down-regulate CD4 do not react or react poorly with thioesterase. An HIV-1 NefLai mutant selected for its lack of interaction with thioesterase was also unable to down-regulate CD4 cell-surface expression. These observations suggest that this human thioesterase is a cellular mediator of Nef-induced CD4 down-regulation.
Keywords: *Antigens, CD4/METABOLISM *Down-Regulation (Physiology) *Gene Products, nef/METABOLISM *HIV-1 *Thiolester Hydrolases/METABOLISMKWDantigens,cd4/metabolismKWDdown-regulation(physiology)KWDgeneproducts,nef/metabolismKWDhiv-1KWDthiolesterhydrolases/metabolism
970930
M9791345

Copyright © 1997 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1997. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .