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Blood, Vol. 93 No. 6 (March 15), 1999:
pp. 1906-1915
From the Dorrance H. Hamilton Laboratories, Center for Human
Virology, Division of Infectious Diseases, Department of Medicine,
Jefferson Medical College, and the Department of Microbiology and
Immunology, Thomas Jefferson University, Philadelphia, PA; and the
Center for Gene Therapy, Allegheny University of the Health Sciences,
Hahnemann Division, Philadelphia, PA.
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.
This article has been cited by other articles:
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| Copyright © 1999 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
