HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization
Details
Serval ID
serval:BIB_CE1A612B8215
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization
Journal
Immunity
ISSN
1074-7613 (Print)
Publication state
Published
Issued date
1994
Volume
1
Number
5
Pages
373-384
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S
Abstract
Nef of primate lentiviruses is required for viremia and progression to AIDS in monkeys. Negative, positive, and no effects of Nef have also been reported on viral replication in cells. To reconcile these observations, we expressed a hybrid CD8-Nef protein in Jurkat cells. Two opposite phenotypes were found, which depended on the intracellular localization of Nef. Expressed in the cytoplasm or on the cell surface, the chimera inhibited or activated early signaling events from the T cell antigen receptor. Activated Jurkat cells died by apoptosis, and only cells with mutated nef genes expressing truncated Nefs survived, which rendered Nef nonfunctional. These mutations paralleled those in other viral strains passaged in vitro. Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation, but they also explain effects of Nef in HIV infection and progression to AIDS
Keywords
Amino Acid Sequence/Animals/Base Sequence/CD8-Positive T-Lymphocytes/chemistry/Gene Products,nef/analysis/Genes,nef/immunology/Hiv-1/genetics/Humans/Hybrid Cells/physiology/Intracellular Fluid/Lymphocyte Activation/Molecular Sequence Data/NF-kappa B/metabolism/Recombinant Fusion Proteins/T-Lymphocytes/Tumor Cells,Cultured/Viral Fusion Proteins/Research
Pubmed
Web of science
Create date
29/01/2008 19:35
Last modification date
20/08/2019 16:48