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Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
HIV-1 Nef increases T cell activation in a stimulus-dependent manner
1Laboratory of Molecular Biology, National Institute of Mental Health, 36 Convent Drive, Bethesda, MD 20892-4034, USA.
Summary
Human immunodeficiency virus Nef protein enhances T cell activation, specifically when stimulated via dual receptors. This finding reveals how Nef lowers activation thresholds, potentially increasing viral replication in vivo.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Lentiviral Nef protein is known to increase viral replication, pathogenesis, and infectivity.
- T cell activation is a critical state for optimal viral replication.
Purpose of the Study:
- To investigate the effect of HIV Nef on T cell activation.
- To determine the mechanism by which Nef influences T cell activation.
Main Methods:
- Studied T cell activation using various mitogens and co-stimulatory signals.
- Assessed interleukin-2 (IL-2) generation as a measure of T cell activation.
- Investigated the role of Nef myristylation in T cell activation.
Main Results:
- HIV Nef enhances T cell activation in a stimulant-dependent manner.
- Nef's enhancement of activation is observed when T cells are stimulated via the T cell receptor and CD28.
- Nef increases the number of fully activated T cells, not the IL-2 secreted per cell.
- Nef-mediated T cell activation is dependent on Nef myristylation.
Conclusions:
- HIV Nef lowers the activation threshold for the dual-receptor T cell activation pathway.
- Nef's ability to boost T cell activity may be significant in vivo, especially when Nef is the primary viral gene product expressed.
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