Association of Alterations in NF-κB Moieties with HIV Type 1 Proviral Latency in Certain Monocytic Cells

Abstract

Human immunodeficiency virus type 1 (HIV-1) replication is controlled by a complex array of virally encoded and cellular proteins. A wide spectrum of levels of HIV-1 expression have been demonstrated in various cells, both in cell culture and in vivo. Molecular mechanisms leading to restricted HIV-1 replication may differ between certain cell types. It is now demonstrated that HIV-1 proviral latency in the monocytic cell line U1, in which only extremely low levels of HIV-1 expression are detected in the baseline unstimulated state, is associated with alterations in nuclear factor-kappa B (NF-κB) moieties demonstrated in these cells by electrophoretic mobility shift assays (EMSAs) and in situ UV cross-linking studies. A predominance of p50 NF-κB moieties and possibly p50 homodimers or closely related species, rather than the p50-p56 heterodimer of NF-κB that is the predominant NF-κB species in most T lymphocytic and monocytic cells, is demonstrated in the nuclei of U1 cells. This pattern of NF-κB-related moieties differs from the latently infected T lymphocytic cell line ACH-2, and from the U937 monocytic line, the parental cell line of the U1 cellular clone. As such, these data suggest that different proximal mechanisms may lead to restricted HIV-1 replication in various cell types.