HIV gp120 induces, NF-kappaB dependent, HIV replication that requires procaspase 8.
BACKGROUND
HIV envelope glycoprotein gp120 causes cellular activation resulting in anergy, apoptosis, proinflammatory cytokine production, and through an unknown mechanism, enhanced HIV replication.


RESULTS
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.


CONCLUSIONS
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.
Bren
Gary D
GD
Division of Infectious Diseases, Mayo Clinic, Rochester, MN, USA.
Trushin
Sergey A
SA
Whitman
Joe
J
Shepard
Brett
B
Badley
Andrew D
AD
D017209:Apoptosis; D001483:Base Sequence; D053181:Caspase 8 / Q000378:metabolism*; D002460:Cell Line; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D016328:NF-kappa B / Q000502:physiology*; D014779:Virus Replication
D017931:DNA Primers; D015699:HIV Envelope Protein gp120; D016328:NF-kappa B; D053181:Caspase 8