HIV-1 Vpr inhibits the maturation and activation of macrophages and dendritic cells in vitro

Muthumani, K., Hwang, D. S., Choo, A. Y., Mayilvahanan, S., Dayes, N. S., Thieu, K. P., Weiner, D. B. (February 2005) HIV-1 Vpr inhibits the maturation and activation of macrophages and dendritic cells in vitro. International Immunology, 17 (2). pp. 103-116. ISSN 0953-8178

URL: http://intimm.oxfordjournals.org/content/17/2/103
DOI: 10.1093/intimm/dxh190

Abstract

Human immunodeficiency virus-1 (HIV-1) Vpr encodes a 14 kDa protein that has been implicated in viral pathogenesis through in vitro modulation of several host cell functions. Vpr modulates cellular proliferation, cell differentiation, apoptosis and host cell transcription in a manner that involves the glucocorticoid pathway. To better understand the role of HIV-1 Vpr in host gene expression, similar to9600 cellular RNA transcripts were assessed for their modulation in primary APC after treatment with a bioactive recombinant Vpr (rVpr) by DNA micro-array. As an extracellular delivered protein, Vpr down-modulated the expression of several immunologically important molecules including CD40, CD80, CD83 and CD86 costimulatory molecules on MDM (monocyte-derived macrophage) and MDDC (monocyte-derived dendritic cells). Maturation of dendritic cells (DC) is known to result in a decreased capacity to produce HIV due to a post-entry block of the HIV-1 replicative cycle. Based on the changes observed in the gene array, we analyzed maturation of DC generated from monocytes in tissue culture as influenced by Vpr. We observed that Vpr-treated immature MDM and MDDC were unable to acquire high levels of costimulatory molecules and failed to develop into mature DC, even in the presence of maturation signals. These studies have importance for understanding the interaction of HIV with the host immune system.

Item Type: Paper
Uncontrolled Keywords: antigen-presenting cells HIV-1 Vpr immune expansion CD40 CD8 HIV-1 micro-array T T cell activation viral clearance and cytokine immunodeficiency virus type 1 cytotoxic T lymphocytes BLOOD mononuclear cells glucocorticoid receptors Rhesis Protein VPR Apoptosis infection antigen anergy
Subjects: diseases & disorders > viral diseases > HIV
diseases & disorders > viral diseases
CSHL Authors:
Depositing User: CSHL Librarian
Date: February 2005
Date Deposited: 06 Jan 2012 19:17
Last Modified: 06 Jan 2012 19:17
URI: http://repository.cshl.edu/id/eprint/22661

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