Human immunodeficiency virus infection of human bone marrow stromal fibroblasts

Abstract

The human immunodeficiency virus (HIV) preferentially infects CD4 positive T cells and monocytes. Other human cell types have been reported to be infectable with HIV, including cells of mesenchymal origin. In this report, we show that both primary human bone marrow stromal fibroblasts and an immortalized human stromal fibroblast line are susceptible to HIV infection. These cells are capable of passing HIV to cells of lymphoid or myeloid lineage, and may thereby act as a reservoir of virus. This in vitro system may be a useful model for assessing the pathophysiology of hematopoietic dysfunction in AIDS patients.

Persistence of Human Parvovirus B19 in Multipotent Mesenchymal Stromal Cells Expressing the Erythrocyte P antigen: Implications for Transplantation

“…Thus, MSC may be a natural reservoir for persistent B19. This is in analogy with the findings of Scadden et al, who described bone marrow stromal cells as a reservoir of HIV, passing the virus to both myeloid and lymphoid cells 34 . Hence, MSC and the bone marrow stroma might be a site of persistent viruses.…”

Intrinsic Human Immunodeficiency Virus Type 1 Resistance of Hematopoietic Stem Cells Despite Coreceptor Expression

“…Chemotherapeutic approaches to treatment of human immunodeficiency virus type 1 (HIV-1) infection have markedly reduced the levels of replicating virus in infected persons and have resulted in clinically demonstrated benefits in patient survival. The extent to which virus suppression leads to improved immune cell parameters is variable (1), however, and impairment of cellular regeneration may be due to alterations in organs of cell development (17,23,32,33), ongoing destruction of highly infectible subsets of developing hematopoietic cells (16,34), or defects in stem cell function (41). Efforts to overcome these abnormalities include the use of cells genetically engineered to be resistant to HIV-1 infection.…”

Granulocyte macrophage colony stimulating factor

“…Several mechanisms have been identified by which HIV infection can result in altered neutrophil development, including, HIV infection of bone marrow stem cells, stroma cells, macrophage and resident CD4 ϩ cells (11,21), altered cytokine milieu in the bone marrow (12), direct suppression of hemopoiesis by viral proteins (13,14), myelosuppressive effects of antiretroviral drugs (15)(16)(17)(18), and infection of the bone marrow by viruses, bacteria or fungi (19,20). Inappropriate activation of neutrophils by opportunistic infections is unlikely because none of the patients had an identified opportunistic infection during the study, nor were bacteria or fungi detected in the blood or bone marrow of FIV-infected animals (data not shown).…”

“…The underlying mechanism for this increased permissiveness to bacterial and fungal infections is poorly understood, but could be related to some developmental defects in neutrophils and other myeloid cells during hemopoiesis. Potential mechanisms resulting in the formation of defective cells include HIV infection of bone marrow stromal macrophage and resident CD4 ϩ cells (11), altered cytokine milieu in the bone marrow (12), direct suppression of hemopoiesis by viral proteins (13,14), myelosuppressive effects of antiretroviral drugs (15)(16)(17)(18), infection of the bone marrow by viruses, bacteria or fungi (19,20), and possibly even HIV infection of hemopoietic stem cells (21). Some form of general therapy, such as the use of hemopoietic factors that promote the formation of myeloid cells, may be of benefit in restoring normal innate immunity.…”