Research
Inhibition of HIV-1 replication in primary human monocytes by the IκB-αS32/36A repressor of NF-κB
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* Corresponding author: Ileana Quinto quinto@unicz.it
1 Department of Clinical and Experimental Medicine, University of Catanzaro "Magna Graecia", Via T. Campanella 115, 88100 Catanzaro, Italy
2 Department of Biochemistry and Medical Biotechnology, University of Naples "Federico II", Via S. Pansini 5, 80131 Naples, Italy
Retrovirology 2004, 1:45 doi:10.1186/1742-4690-1-45
Published: 21 December 2004Abstract
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-κB transacting factors strongly enhance the HIV/SIV expression in both epithelial and lymphoid cells. Controversial results have been reported on the requirement of NF-κB factors in distinct cell reservoirs, such as CD4-positive T lymphocytes and monocytes. We have previously shown that IκB-αS32/36A, a proteolysis-resistant inhibitor of NF-κB, 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)IκB-αS32/36A, a macrophage-tropic HIV-1 recombinant strain endowed to express IκB-αS32/36A.
Results
In this work, we show that infection with NL(AD8)IκB-αS32/36A down-regulated the NF-κB DNA binding activity in cells. NL(AD8)IκB-αS32/36A was also highly attenuated for replication in cultures of human primary monocytes.
Conclusions
These results point to a major requirement of NF-κB activation for the optimal replication of HIV-1 in monocytes and suggest that agents which interfere with NF-κB activity could counteract HIV-1 infection of monocytes-macrophages in vivo.