Journal
PLOS ONE
Volume 3, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0002112
Keywords
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Categories
Funding
- National Institutes of Health [R01 AI62261, R01 AI40384, R21DK 77575-1]
- Burroughs Wellcome Fund's Clinical Scientist Award in Translational Research [1005160]
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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-kappa B activation, (2) caspase 8 dependent apoptosis, and that (3) caspase 8 directly activates NF-kappa B, we questioned whether these three events might be interrelated. We first show that HIV-1 infected T cell apoptosis, NF-kappa B 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-kappa B activity. Finally, we demonstrate that the HIV protease cleavage of caspase 8 is necessary for optimal NF-kappa B activation and that the HIV-1 protease specific cleavage fragment Casp8p41 is sufficient to stimulate HIV-1 replication through NF-kappa B 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.
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