Retinoid-Dependent Restriction of Human Immunodeficiency Virus Type 1 Replication in Monocytes/Macrophages

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

“…Interestingly, the selective glucocorticoid modulator RU-486, which acts as an antagonist for GR-mediated gene transactivation but as an agonist for GR- Ligand-activated NRs acutely repress HIV-1 expression. As a next step in defining the mechanisms of GR-, PPAR␥-, and LXR-mediated repression, we determined whether the individual ligands could inhibit HIV-1 expression acutely when added at the same time as TLR ligands or whether repression required pretreatment as shown previously for RAR (57). We found that all ligands repressed HIV-1 when the MDMs were pretreated for 24 h prior to the addition of PAM3CSK4 (Fig.…”

“…NRs are potent bifunctional modulators of gene expression, capable of either activating or repressing gene expression. It is known that certain NRs, such as RAR, inhibit HIV-1 transcription (21,57,61,77,78,82,106,133,142). We wanted to determine whether GR, PPAR␥, and LXR signaling affected HIV-1 transcription.…”

“…We, and others, have found that ligand-activated retinoic acid receptor (RAR) represses HIV-1 transcription in both cultured monocytic cell lines and primary monocyte-derived macrophages (MDMs) through the induction of an as-yet-unidentified factor (21,57,77,97). Previous studies have also demonstrated that the ubiquitously expressed GR can inhibit HIV-1 replication in certain myeloid and lymphoid cell lines (78,82,106,133) but not in others (79,81,84).…”

“…Second, STIs cause inflammation that leads to the recruitment of immune cells to the site of inflammation, thereby increasing the size of the HIV-1 target cell population (88,128,136). Third, STIs promote a favorable local environment for HIV-1 replication both by directly activating HIV-1 target cells and by inducing the release of cytokines that favor virus replication through the engagement of Toll-like receptors (TLRs) and other innate immune sensors in cells present in the mucosa (9,10,37,57,75,122,134,145,146,161).…”

Retrovirus Infection and Retinoid

“…Maciaszek et al reported that ATRA repressed HIV-1 long terminal repeat-directed expression in THP-1 monocytes (Maciaszek et al, 1998). Furthermore, Hanley et al reported that a synthetic pan-retinoic acid receptor antagonist, BMS-204 493, activated replication of HIV-1 in a dosedependent manner (Hanley et al, 2004). This phenomenon suggested that ATRA-induced transactivation of cellular gene expression is required for the viral replication (Recio et al, 2000).…”