Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development

Stove, V., Naessens, E., Stove, C., Swigut, T., Plum, J., Verhasselt, B. (October 2003) Signaling but not trafficking function of HIV-1 protein Nef is essential for Nef-induced defects in human intrathymic T-cell development. Blood, 102 (8). pp. 2925-2932. ISSN 0006-4971

Abstract

The HIV-1 gene nef is important for progression toward AIDS and cellular depletion of the infected thymus. Expression of the Nef protein alone impairs human thymopoiesis. Here, we performed a structure-function analysis of the Nef protein by comparing the effect on T-cell development of different nef alleles, either wild type or defective for selected functions, expressed by human thymocytes. We show that Nef-mediated impaired thymopoiesis is not due to altered surface marker trafficking, nor dependent on oligomerization of Nef. By contrast, mutations in the myristoylation site and in signaling sites of Nef, ie, sites important for interaction with phosphofurin acidic cluster sorting protein-1 (PACS-1), Src homology domain 3 (SH3) domains, and p21-activated kinase 2 (PAK2), were found to be critical for its effect on T-cell development. These results point to sites in Nef to target therapeutically for restoration of thymopoiesis in HIV infection. (Blood. 2003;102:2925-2932) (C) 2003 by The American Society of Hematology.

Item Type:	Paper
Uncontrolled Keywords:	IMMUNODEFICIENCY-VIRUS TYPE-1 CD4 DOWN-REGULATION SCID-HU MICE IN-VIVO TRANSGENIC MICE DILEUCINE MOTIF GENE-EXPRESSION SURFACE CD4 SH3 DOMAIN BINDING SURFACE
Subjects:	organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organism description > virus
CSHL Authors:	Swigut, Tomek
Communities:	CSHL labs > Skowronski lab
Depositing User:	Matt Covey
Date:	October 2003
Date Deposited:	11 Jun 2013 16:40
Last Modified:	11 Jun 2013 16:40
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27956

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