CD28-dependent HIV-1 transcription is associated with Vav, Rac, and NF-κB activation

Julie A. Cook, Lee Albacker, Avery August, Andrew J. Henderson

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Activation of HIV-1-infected T cells through the T cell receptor and costimulatory molecule CD28 induces proviral transcription; however, the mechanism behind this enhanced virus expression is unknown. Jurkat T cells and primary CD4+ T cells expressing a CD8α/CD28 chimeric receptor containing a mutation at tyrosine 200 in the cytoplasmic tail were unable to fully induce HIV-1 proviral transcription in response to CD8α/28 receptor cross-linking in comparison to CD28 costimulation. The loss of transactivation seen with the mutant chimeric receptor correlated with a decrease in Vav tyrosine phosphorylation. CD28-dependent activation of HIV-1 transcription also required the GTPase activity of Rac1, which was not activated during costimulation with the mutated receptor. Furthermore, the mutated receptor was unable to induce NF-κB DNA binding or transactivation, as demonstrated by electromobility shift assays and HIV-1 long terminal repeat and NF-κB-dependent reporter constructs. These studies show that signaling events initiated by tyrosine 200 of CD28 are required for efficient expression of HIV-1 transcription in activated T cells.

Original languageEnglish (US)
Pages (from-to)35812-35818
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number37
DOIs
StatePublished - Sep 12 2003

Fingerprint

T-cells
Transcription
HIV-1
Chemical activation
Tyrosine
T-Lymphocytes
Costimulatory and Inhibitory T-Cell Receptors
Transcriptional Activation
Phosphorylation
HIV Long Terminal Repeat
Terminal Repeat Sequences
GTP Phosphohydrolases
Viruses
Jurkat Cells
Assays
Molecules
DNA
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cook, Julie A. ; Albacker, Lee ; August, Avery ; Henderson, Andrew J. / CD28-dependent HIV-1 transcription is associated with Vav, Rac, and NF-κB activation. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 37. pp. 35812-35818.
@article{c3cb2ffa202b43c98b39747a6bd52ed3,
title = "CD28-dependent HIV-1 transcription is associated with Vav, Rac, and NF-κB activation",
abstract = "Activation of HIV-1-infected T cells through the T cell receptor and costimulatory molecule CD28 induces proviral transcription; however, the mechanism behind this enhanced virus expression is unknown. Jurkat T cells and primary CD4+ T cells expressing a CD8α/CD28 chimeric receptor containing a mutation at tyrosine 200 in the cytoplasmic tail were unable to fully induce HIV-1 proviral transcription in response to CD8α/28 receptor cross-linking in comparison to CD28 costimulation. The loss of transactivation seen with the mutant chimeric receptor correlated with a decrease in Vav tyrosine phosphorylation. CD28-dependent activation of HIV-1 transcription also required the GTPase activity of Rac1, which was not activated during costimulation with the mutated receptor. Furthermore, the mutated receptor was unable to induce NF-κB DNA binding or transactivation, as demonstrated by electromobility shift assays and HIV-1 long terminal repeat and NF-κB-dependent reporter constructs. These studies show that signaling events initiated by tyrosine 200 of CD28 are required for efficient expression of HIV-1 transcription in activated T cells.",
author = "Cook, {Julie A.} and Lee Albacker and Avery August and Henderson, {Andrew J.}",
year = "2003",
month = "9",
day = "12",
doi = "10.1074/jbc.M302878200",
language = "English (US)",
volume = "278",
pages = "35812--35818",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "37",

}

CD28-dependent HIV-1 transcription is associated with Vav, Rac, and NF-κB activation. / Cook, Julie A.; Albacker, Lee; August, Avery; Henderson, Andrew J.

In: Journal of Biological Chemistry, Vol. 278, No. 37, 12.09.2003, p. 35812-35818.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CD28-dependent HIV-1 transcription is associated with Vav, Rac, and NF-κB activation

AU - Cook, Julie A.

AU - Albacker, Lee

AU - August, Avery

AU - Henderson, Andrew J.

PY - 2003/9/12

Y1 - 2003/9/12

N2 - Activation of HIV-1-infected T cells through the T cell receptor and costimulatory molecule CD28 induces proviral transcription; however, the mechanism behind this enhanced virus expression is unknown. Jurkat T cells and primary CD4+ T cells expressing a CD8α/CD28 chimeric receptor containing a mutation at tyrosine 200 in the cytoplasmic tail were unable to fully induce HIV-1 proviral transcription in response to CD8α/28 receptor cross-linking in comparison to CD28 costimulation. The loss of transactivation seen with the mutant chimeric receptor correlated with a decrease in Vav tyrosine phosphorylation. CD28-dependent activation of HIV-1 transcription also required the GTPase activity of Rac1, which was not activated during costimulation with the mutated receptor. Furthermore, the mutated receptor was unable to induce NF-κB DNA binding or transactivation, as demonstrated by electromobility shift assays and HIV-1 long terminal repeat and NF-κB-dependent reporter constructs. These studies show that signaling events initiated by tyrosine 200 of CD28 are required for efficient expression of HIV-1 transcription in activated T cells.

AB - Activation of HIV-1-infected T cells through the T cell receptor and costimulatory molecule CD28 induces proviral transcription; however, the mechanism behind this enhanced virus expression is unknown. Jurkat T cells and primary CD4+ T cells expressing a CD8α/CD28 chimeric receptor containing a mutation at tyrosine 200 in the cytoplasmic tail were unable to fully induce HIV-1 proviral transcription in response to CD8α/28 receptor cross-linking in comparison to CD28 costimulation. The loss of transactivation seen with the mutant chimeric receptor correlated with a decrease in Vav tyrosine phosphorylation. CD28-dependent activation of HIV-1 transcription also required the GTPase activity of Rac1, which was not activated during costimulation with the mutated receptor. Furthermore, the mutated receptor was unable to induce NF-κB DNA binding or transactivation, as demonstrated by electromobility shift assays and HIV-1 long terminal repeat and NF-κB-dependent reporter constructs. These studies show that signaling events initiated by tyrosine 200 of CD28 are required for efficient expression of HIV-1 transcription in activated T cells.

UR - http://www.scopus.com/inward/record.url?scp=0042316801&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042316801&partnerID=8YFLogxK

U2 - 10.1074/jbc.M302878200

DO - 10.1074/jbc.M302878200

M3 - Article

C2 - 12842899

AN - SCOPUS:0042316801

VL - 278

SP - 35812

EP - 35818

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 37

ER -