AI Article Synopsis
- HIV-1 infection of resting peripheral mononuclear blood cells (PBMCs) is hindered due to a block in the integration of the provirus into the host genome, linked to the glucocorticoid receptor (GR) status.
- The addition of a GR ligand enhances proviral integration, but this effect is limited to a short time after infection and relies on both GR and the viral protein Vpr.
- GR and Vpr initially localize in the cytoplasm and migrate to the nucleus when a ligand is added, indicating that the cytoplasmic presence of GR inhibits HIV replication, while steroids can increase the number of virus-producing cells.
Article Abstract
Infection of resting peripheral mononuclear blood cells (PBMCs) with HIV-1 is not productive due to a block prior to integration of the provirus into the host genome. Here we show that a unique restriction is determined by the status of the glucocorticoid receptor (GR). Proviral integration increases after addition of a GR ligand. The ligand dependent effect is confined to an early time period after infection and requires GR and the GR binding viral protein Vpr. Endogenous GR and transiently expressed Vpr are localized in the cytoplasm in unstimulated PMCs and comigrate into the nucleus upon ligand addition. Thus, the predominant cytoplasmic localization of GR seems to be a specific obstacle for HIV replication. Accordingly, efficient proviral integration in a cell line with a constitutive cytoplasmic GR requires addition of a GR ligand. The data suggest that steroids can overcome the restriction on HIV provirus formation and thereby increase the reservoir of virus producing cells.
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| http://dx.doi.org/10.1016/j.virol.2008.01.037 | DOI Listing |
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