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Open Access Research

Cellular phenotype impacts human immunodeficiency virus type 1 viral protein R subcellular localization

Adriano Ferrucci123, Michael R Nonnemacher23 and Brian Wigdahl23*

Author Affiliations

1 School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104, USA

2 Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA

3 Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA 19102, USA

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Virology Journal 2011, 8:397  doi:10.1186/1743-422X-8-397

Published: 10 August 2011

Abstract

Background

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) is a virion-associated regulatory protein that functions at several points within the viral life cycle and has been shown to accumulate primarily in the nucleus and at the nuclear envelope. However, most studies have investigated Vpr localization employing cell types irrelevant to HIV-1 pathogenesis. To gain a better understanding of how cellular phenotype might impact HIV-1 Vpr intracellular localization, Vpr localization was examined in several cell lines representing major cellular targets for HIV-1 infection within the peripheral blood, bone marrow, and central nervous system (CNS).

Results

Utilizing a green fluorescent protein-tagged Vpr, we detected Vpr mainly in foci inside the nucleus, at the nuclear envelope, and around the nucleoli, with dispersed accumulation in the cytoplasm of human endothelial kidney 293T cells. No differences were observed in Vpr localization pattern with respect to either the location of the tag (N- or C-terminus) or the presence of other viral proteins. Subsequently, the Vpr localization pattern was explored in two primary HIV-1 target cells within the peripheral blood: the CD4+ T lymphocyte (represented by the Jurkat CD4+ T-cell line) and the monocyte-macrophage (represented by the U-937 cell line). Vpr was found primarily in speckles within the cytoplasm of the Jurkat T cells, whereas it accumulated predominantly intranuclearly in U-937 monocytic cells. These patterns differ from that observed in a bone marrow progenitor cell line (TF-1), wherein Vpr localized mainly at the nuclear envelope with some intranuclear punctuate staining. Within the CNS, we examined two astroglioma cell lines and found that Vpr displayed a perinuclear and cytoplasmic distribution.

Conclusions

The results suggest that the pattern of Vpr localization depends on cellular phenotype, probably owing to interactions between Vpr and cell type-specific host factors. These interactions, in turn, are likely coupled to specific roles that Vpr plays in each cell type within the context of the viral life cycle. Phenotype-specific Vpr localization patterns might also provide an explanation with respect to Vpr secretion or release from HIV-1-infected cells within the peripheral blood and CNS.

Keywords:
HIV-1; Vpr; localization pattern; phenotype; CD4+ T lymphocytes; monocytic cells; bone marrow progenitor cells; astrocytes