Pathogenesis of HIV-1 infection within bone marrow cells

Mononuclear phagocytic cells and CD4+ T lymphocytes represent the major targets for infectionby HIV-1 in vivo. The most severe pathogenic features associated with HIV-1 infectioncan be attributed to malfunction or premature death of these cells that are of hematopoieticorigin. Patients with acquired immunodeficiency syndrome (AIDS), suffer from many hematologicdisorders, particularly those persons with long-term infection of HIV-1. These disordersinclude anemia, lymphocytopenia, thrombocytopenia and neutropenia. The mechanismsthat lead to the induction of these disorders are multi-factorial. However, sufficient evidencehas accumulated which suggests that HIV- 1 infection of cells within the microenvironment ofthe bone marrow can lead to the induction of hematopoietic deficits. Most studies indicatethat marrow-derived hematopoeitic stem cells cannot be infected by HIV-1 until they undergomodest differentiation in order to express the appropriate receptors to enable virus entry andsubsequent replication. Some cells within the mixed environment of the marrow stromaappear to support HIV-1 replication however. These cells include marrow microvascularendothelial cells, sometimes referred to as blanket cells, stromal fibroblasts, as well as mononuclearphagocytes. Our recent experiments suggest that the HIV-1 accessory protein, Vpr,plays some role in the activation of marrow-derived mononuclear phagocytes which appearsto result in premature phagocytosis of non-adherent marrow cells present in the in vitro cultures.This phenomenon could account, in part, for the induction of cytopenias that are typicalof individuals infected by HIV-1.