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.