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

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

Research output: Contribution to journalArticle

22 Scopus citations

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

ASJC Scopus subject areas

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

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