Inhibition of HIV-1 replication in primary human monocytes by the IkappaB-alphaS32/36A repressor of NF-kappaB.
BACKGROUND
The identification of the molecular mechanisms of human immunodeficiency virus type 1, HIV-1, transcriptional regulation is required to develop novel inhibitors of viral replication. NF-kappaB transacting factors strongly enhance the HIV/SIV expression in both epithelial and lymphoid cells. Controversial results have been reported on the requirement of NF-kappaB factors in distinct cell reservoirs, such as CD4-positive T lymphocytes and monocytes. We have previously shown that IkappaB-alphaS32/36A, a proteolysis-resistant inhibitor of NF-kappaB, potently inhibits the growth of HIV-1 and SIVmac239 in cell cultures and in the SIV macaque model of AIDS. To further extend these observations, we have generated NL(AD8)IkappaB-alphaS32/36A, a macrophage-tropic HIV-1 recombinant strain endowed to express IkappaB-alphaS32/36A.


RESULTS
In this work, we show that infection with NL(AD8)IkappaB-alphaS32/36A down-regulated the NF-kappaB DNA binding activity in cells. NL(AD8)IkappaB-alphaS32/36A was also highly attenuated for replication in cultures of human primary monocytes.


CONCLUSIONS
These results point to a major requirement of NF-kappaB activation for the optimal replication of HIV-1 in monocytes and suggest that agents which interfere with NF-kappaB activity could counteract HIV-1 infection of monocytes-macrophages in vivo.
Palmieri
Camillo
C
Department of Clinical and Experimental Medicine, University of Catanzaro Magna Graecia, Via T. Campanella 115, 88100 Catanzaro, Italy. cpalmieri@unicz.it
Trimboli
Francesca
F
Puca
Antimina
A
Fiume
Giuseppe
G
Scala
Giuseppe
G
Quinto
Ileana
I
D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000502:physiology*; D009000:Monocytes / Q000821:virology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D019713:Receptors, CCR5 / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics; D015183:Restriction Mapping; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D014779:Virus Replication / Q000502:physiology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D000072000:NF-KappaB Inhibitor alpha