title: HIV-1 Vpr inhibits the maturation and activation of macrophages and dendritic cells in vitro.
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, approximately 9600 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, PA 19104, USA.
authors.forename: Karuppiah
authors.initials: K
authors.lastname: Muthumani
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Hwang
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Choo
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Mayilvahanan
authors.forename: Nathanael S
authors.initials: NS
authors.lastname: Dayes
authors.forename: Khanh P
authors.initials: KP
authors.lastname: Thieu
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling; D016336:Gene Products, vpr / Q000235:genetics / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000235:genetics / Q000502:physiology*; D014771:Virion / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus
chemical_list: D000943:Antigens, Differentiation; D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus