Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-I LTR dependent expression

Background: In HIV-infected T lymphocytes, NF-kappa B/Rel transcription factors are major elements involved in the activation of LTR-dependent transcription from latency. Most NF-kappa B heterodimer p65/p50 is sequestered as an inactive form in the cytoplasm of resting T lymphocytes via its interaction with I kappa B inhibitors. In these cells, both absolute HIV latency and low level ongoing HIV replication have been described. These situations could be related to differences in the balance between NF-kappa B and I kappa B alpha ratio. Actually, control of I kappa B alpha by cellular factors such as Murr-I plays a critical role in maintaining HIV latency in unstimulated T lymphocytes. Formerly, our group demonstrated the presence of nuclear I kappa B alpha in T cells after PMA activation. Now we attempt to determine the dynamics of NF-kappa B/I kappa B alpha nucleocytosolic transport in absence of activation as a mechanism to explain both the maintenance of latency and the existence of low level ongoing HIV replication in resting CD4+ T lymphocytes. Results and conclusion: We show that the inhibition of the nuclear export by leptomycin B in resting CD4+ T cells resulted in nuclear accumulation of both I kappa B alpha and p65/RelA, as well as formation of NF-kappa B/I kappa B alpha complexes. This proves the existence of a rapid shuttling of I kappa B alpha between nucleus and cytosol even in absence of cellular activation. The nuclear accumulation of I kappa B alpha in resting CD4+ T lymphocytes results in inhibition of HIV-LTR dependent transcription as well as restrains HIV replication in CD4+ T lymphocytes. On the other hand, basal NF-kappa B activity detected in resting CD4+ T lymphocytes was related to low level HIV replication in these cells.