Infected cell killing by HIV-1 protease promotes NF-κB dependent HIV-1 replication

Gary D. Bren, Joe Whitman, Nathan W Cummins, Brett Shepard, Stacey A. Rizz, Sergey A. Trushin, Andrew David Badley

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Acute HIV-1 infection of CD4 T cells often results in apoptotic death of infected cells, yet is unclear what evolutionary advantage this offers to HIV-1. Given the independent observations that acute T cell HIV-1 infection results in (1) NF-κB activation, (2) caspase 8 dependent apoptosis, and that (3) caspase 8 directly activates NF-κB, we questioned whether these three events might be interrelated. We first show that HIV-1 infected T cell apoptosis, NF-κB activation, and caspase 8 cleavage by HIV-1 protease are coincident. Next we show that HIV-1 protease not only cleaves procaspase 8, producing Casp8p41, but also independently stimulates NF-κB activity. Finally, we demonstrate that the HIV protease cleavage of caspase 8 is necessary for optimal NF-κB activation and that the HIV-1 protease specific cleavage fragment Casp8p41 is sufficient to stimulate HIV-1 replication through NF-κB dependent HIV-LRT activation both in vitro as well as in cells from HIV infected donors. Consequently, the molecular events which promote death of HIV-1 infected T cells function dually to promote HIV-1 replication, thereby favoring the propagation and survival of HIV-1.

Original languageEnglish (US)
Article numbere2112
JournalPLoS One
Volume3
Issue number5
DOIs
StatePublished - May 7 2008

Fingerprint

Caspase 8
Human immunodeficiency virus 1
T-cells
HIV-1
proteinases
Cells
Chemical activation
caspase-8
cells
T-Lymphocytes
T-lymphocytes
HIV Protease
Apoptosis
HIV Infections
HIV
Human immunodeficiency virus 1 p16 protease
apoptosis
Cell Death
infection
cell death

ASJC Scopus subject areas

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

Cite this

Infected cell killing by HIV-1 protease promotes NF-κB dependent HIV-1 replication. / Bren, Gary D.; Whitman, Joe; Cummins, Nathan W; Shepard, Brett; Rizz, Stacey A.; Trushin, Sergey A.; Badley, Andrew David.

In: PLoS One, Vol. 3, No. 5, e2112, 07.05.2008.

Research output: Contribution to journalArticle

Bren, Gary D. ; Whitman, Joe ; Cummins, Nathan W ; Shepard, Brett ; Rizz, Stacey A. ; Trushin, Sergey A. ; Badley, Andrew David. / Infected cell killing by HIV-1 protease promotes NF-κB dependent HIV-1 replication. In: PLoS One. 2008 ; Vol. 3, No. 5.
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