Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Human immunodeficiency virus type 1 Vpr alters bone marrow cell function.
Blood. 1999 Mar 15;93(6):1906-15. Unique Identifier : AIDSLINE MED/99168978 Kulkosky J; Laptev A; Shetty S; Srinivasan A; BouHamdan M; Prockop DJ; Pomerantz RJ; Dorrance H. Hamilton Laboratories, Center for Human Virology,; Division of Infectious Diseases, Department of Medicine,; Jefferson Medical College, Jefferson University, Philadelphia,; PA, USA.
Abstract:
Vpr, a 96 amino acid protein, encoded by the human immunodeficiency virus type I (HIV-1), is important for efficient infection of mononuclear phagocytic cells. These cells are abundant in whole bone marrow, which can easily be cultured in vitro to support hematopoiesis. Our experiments indicate that Vpr plays a role in the potent activation of murine and human mononuclear phagocytic cells within a hematopoietic microenvironment. In murine cultures, avid erythrophagocytosis is triggered by transduction of marrow cells with supernatant derived from PA317 cells transfected with a murine retroviral delivery vector bearing a Vpr expression cassette. Supernatants derived from cells transfected with the same vector carrying sequences for the expression of other relevant viral and nonviral proteins do not induce erythrophagocytosis to any marked degree. The effect on human marrow cells is similar, where treatment promotes adhesion of mononuclear phagocytic cells to culture plates in association with other nucleated and nonnucleated cells that undergo subsequent engulfment. The differential effects of Vpr point and deletion mutants in both marrow culture systems fortify the view that the effect is specific to HIV-1 Vpr. Addition of low molar quantities of purified Vpr to marrow cultures is also capable of promoting cell adhesion and phagocytosis, suggesting that extracellular Vpr is the effector of the phenomenon. Accelerated phagocytosis is a hallmark of promonocyte, monocyte, and macrophage activation and its occurrence within a hematopoietic microenvironment may account for critical in vivo pathogenic features of HIV-1 infection. First, activation of mononuclear phagocytes may promote productive viral infection; and second, premature phagocytosis could provide, at least in part, a molecular explanation for the induction of the idiopathic cytopenias that are typical of individuals infected with HIV-1.
Keywords: JOURNAL ARTICLE Acquired Immunodeficiency Syndrome/PATHOLOGY Animal Bone Marrow Cells/*PHYSIOLOGY Cell Adhesion Cell Line Erythrocytes Gene Products, vpr/*GENETICS/PHARMACOLOGY/PHYSIOLOGY Genetic Vectors Glutathione Transferase/GENETICS/PHARMACOLOGY Human *HIV-1 Mice Phagocytosis Recombinant Fusion Proteins/PHARMACOLOGY Retroviridae/GENETICS Transfection 990630
A9960995
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Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
