Pathogenesis of HIV-1 infection within bone marrow cells

Mononuclear phagocytic cells and CD4+ T lymphocytes represent the major tar gets for infection by HIV-1 in vivo. Tine most severe pathogenic features a ssociated with HIV-1 infection can be attributed to malfunction or prematur e death of these cells that are of hematopoietic origin. Patients with acqu ired immunodeficiency syndrome (AIDS), suffer from many hematologic disorde rs, particularly those persons with long-term infection of HIV-I. These dis orders include anemia, lymphocytopenia, thrombocytopenia and neutropenia. T he mechanisms that lead to the induction of these disorders are multi-facto rial. However, sufficient evidence has accumulated which suggests that HIV- 1 infection of cells within the microenvironment of the bone marrow can lea d to the induction of hematopoietic deficits. Most studies indicate that ma rrow-derived hematopoeitic stem cells cannot be infected by HIV-1 until the y undergo modest differentiation in order to express the appropriate recept ors to enable virus entry and subsequent replication. Some cells within the mixed environment of the marrow stroma appear to support HIV-1 replication however. These cells include marrow microvascular endothelial cells, somet imes referred to as blanket cells, stromal fibroblasts, as well as mononucl ear phagocytes. Our recent experiments suggest that the HIV-1 accessory pro tein, Vpr. plays some role in the activation of marrow-derived mononuclear phagocytes which appears to result in premature phagocytosis of non-adheren t marrow cells present in the in vitro cultures. This phenomenon could acco unt, in part, for the induction of cytopenias that are typical of individua ls infected by HIV-1.