Altered T-Cell Activation and Development in Transgenic Mice Expressing the Hiv-1 Nef Gene

Skowronski, J., Parks, D., Mariani, R. (February 1993) Altered T-Cell Activation and Development in Transgenic Mice Expressing the Hiv-1 Nef Gene. Embo J, 12 (2). pp. 703-713. ISSN 0261-4189

URL: http://www.ncbi.nlm.nih.gov/pubmed/8095017

Abstract

The nef gene, which encodes related cytoplasmic proteins in both human (HIV) and simian (SIV) immunodeficiency viruses is dispensable for viral replication in vitro. In contrast, in vivo experiments have revealed that SIV nef is required for efficient viral replication and development of AIDS in SIV infected rhesus monkeys, thus indicating that nef plays an essential role in the natural infection. We show that expression of the Nef protein from the HIV-1 NL43 isolate in transgenic mice perturbs development of CD4+ T cells in the thymus and elicits depletion of peripheral CD4+ T cells. Thymic T cells expressing NL43 Nef show altered activation responses. In contrast, Nef protein of the HIV-1 HxB3 isolate does not have an overt effect on T cells when expressed in transgenic animals. The differential effects of the two HIV-1 nef alleles in transgenic mice correlate with down-regulation of CD4 antigen expression on thymic T cells. The differential interactions of the NL43 and HxB3 nef alleles with CD4 were reproduced in a transient assay in human CD4+ CEM T cells. Down-regulation of CD4 by nef in both human and transgenic murine T cells indicates that the relevant interactions are conserved in these two systems and suggests that the consequences of Nef expression on the host cell function can be analyzed in vivo in the murine system. Our observations from transgenic mice suggest that nef-elicited perturbations in T cell signalling play an important role in the viral life cycle in vivo, perhaps resulting in elimination of infected CD4+ T cells.

Item Type: Paper
Uncontrolled Keywords: AIDS CD4 HIV NEF T-CELL ACTIVATION HUMAN-IMMUNODEFICIENCY-VIRUS OPEN READING FRAME MONOCLONAL-ANTIBODY CD4 RECEPTOR MOLECULES DEPLETION INFECTION PROTEIN ANTIGEN
Subjects: diseases & disorders > viral diseases > HIV
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

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal
CSHL Authors:
Communities: CSHL labs > Skowronski lab
Depositing User: Matt Covey
Date: February 1993
Date Deposited: 19 Apr 2016 20:43
Last Modified: 19 Apr 2016 20:43
PMCID: PMC413256
URI: http://repository.cshl.edu/id/eprint/32507

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