Human immunodeficiency virus type 1 Vpr alters bone marrow cell function

Vpr, a 96 amino acid protein, encoded by the human immunodeficiency virus t ype I (HIV-4). is important for efficient infection of mononuclear phagocyt ic cells. These cells are abundant in whole bone marrow, which can easily b e 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 culture s, avid erythrophagocytosis is triggered by transduction of marrow cells wi th supernatant derived from PA317 cells transfected with a murine retrovira l delivery vector bearing a Vpr expression cassette. Supernatants derived f rom cells transfected with the same vector carrying sequences for the expre ssion of other relevant viral and nonviral proteins do not induce erythroph agocytosis to any marked degree. The effect on human marrow cells is simila r, where treatment promotes adhesion of mononuclear phagocytic cells to cul ture plates in association with other nucleated and nonnucleated cells that undergo subsequent engulfment. The differential effects of Vpr point and d eletion mutants in both marrow culture systems fortify the view that the ef fect 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 phag ocytosis, suggesting that extracellular Vpr is the effector of the phenomen on. Accelerated phagocytosis is a hallmark of promonocyte, monocyte, and ma crophage activation and its occurrence within a hematopoietic microenvironm ent 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 pa rt, a molecular explanation for the induction of the idiopathic cytopenias that are typical of individuals infected with HIV-1. (C) 1999 by The Americ an Society of Hematology.