HIV gp120 Induces, NF-κB Dependent, HIV Replication that Requires Procaspase 8
| Autor: | Andrew D. Badley, Brett D. Shepard, Sergey Trushin, Joe Whitman, Gary D. Bren |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Immunology
lcsh:Medicine Apoptosis Electrophoretic Mobility Shift Assay Biology HIV Envelope Protein gp120 Caspase 8 Virus Replication Proinflammatory cytokine Cell Line 03 medical and health sciences chemistry.chemical_compound Humans lcsh:Science 030304 developmental biology DNA Primers HIV Long Terminal Repeat 0303 health sciences Multidisciplinary Base Sequence Hydrolysis lcsh:R 030302 biochemistry & molecular biology NF-kappa B CD28 virus diseases NF-κB Infectious Diseases/HIV Infection and AIDS NFKB1 Molecular biology 3. Good health Infectious Diseases Viral replication chemistry Cancer research HIV-1 lcsh:Q Tumor necrosis factor alpha Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 4, Iss 3, p e4875 (2009) |
| ISSN: | 1932-6203 |
| Popis: | 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 kappaB (NF-kappaB), in a manner which is inhibited by dominant negative IkappaBalpha. This caspase 8 dependent NF-kappaB activation occurs following stimulation with gp120, TNF, or CD3/CD28 crosslinking, but these treatments do not activate NF-kappaB in cells deficient in caspase 8. The Casp8p43 cleavage fragment also transactivates the HIV LTR through NF-kappaB, and the absence of caspase 8 following HIV infection greatly inhibits HIV replication. CONCLUSION/SIGNIFICANCE Gp120 induced caspase 8 dependent NF-kappaB 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. |
| Databáze: | OpenAIRE |
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