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- Title
Infected Cell Killing by HIV-1 Protease Promotes NF-kB Dependent HIV-1 Replication.
- Authors
Bren, Gary D.; Whitman, Joe; Cummins, Nathan; Shepard, Brett; Rizza, Stacey A.; Trushin, Sergey A.; Badley, Andrew D.
- Abstract
Acute HIV-1 infection of CD4 T cells often results in apoptotic death of infected cells, yet it 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-LTR 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.
- Subjects
HIV infections; PROTEOLYTIC enzymes; VIRAL replication; T cells; CELL death; CELL culture; ANTIGENS; GLUTAMINE; LIPIDS
- Publication
PLoS ONE, 2008, Vol 3, Issue 5, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0002112