HIV gp120 induces, NF-κB dependent, HIV replication that requires procaspase 8

Gary D. Bren, Sergey A. Trushin, Joe Whitman, Brett Shepard, Andrew David Badley

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: HIV envelope glycoprotein gp120 causes cellular activation resulting in anergy, apoptosis, proinflammatory cytokine production, and through an unknown mechanism, enhanced HIV replication. Methodology/Principal Findings: We describe that the signals which promote apoptosis are also responsible for the enhanced HIV replication. Specifically, we demonstrate that the caspase 8 cleavage fragment Caspase8p43, activates p50/p65 Nuclear Factor κB (NF-κB), in a manner which is inhibited by dominant negative IkBα. This caspase 8 dependent NF-κB activation occurs following stimulation with gp120, TNF, or CD3/CD28 crosslinking, but these treatments do not activate NF-κB in cells deficient in caspase 8. The Casp8p43 cleavage fragment also transactivates the HIV LTR through NF-κB, and the absence of caspase 8 following HIV infection greatly inhibits HIV replication. Conclusion/Significance: Gp120 induced caspase 8 dependent NF-κB activation is a novel pathway of HIV replication which increases understanding of the biology of T-cell death, as well as having implications for understanding treatment and prevention of HIV infection.

Original languageEnglish (US)
Article numbere4875
JournalPLoS One
Volume4
Issue number3
DOIs
StatePublished - Mar 16 2009

Fingerprint

HIV Envelope Protein gp120
caspase-8
Caspase 8
HIV
Chemical activation
HIV infections
HIV Infections
apoptosis
Apoptosis
T-cells
Cell death
crosslinking
Crosslinking
B-lymphocytes
cell death
glycoproteins
Cell Death
cytokines
T-lymphocytes
Cytokines

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

HIV gp120 induces, NF-κB dependent, HIV replication that requires procaspase 8. / Bren, Gary D.; Trushin, Sergey A.; Whitman, Joe; Shepard, Brett; Badley, Andrew David.

In: PLoS One, Vol. 4, No. 3, e4875, 16.03.2009.

Research output: Contribution to journalArticle

Bren, Gary D. ; Trushin, Sergey A. ; Whitman, Joe ; Shepard, Brett ; Badley, Andrew David. / HIV gp120 induces, NF-κB dependent, HIV replication that requires procaspase 8. In: PLoS One. 2009 ; Vol. 4, No. 3.
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