Enhanced HIV-1 activity in bone marrow can lead to myelopoietic suppression partially contributed by gag p24.
Similar to other lymphoid organs, the bone marrow (BM) is a potential reservoir for HIV-1. Although hematologic abnormalities are common in AIDS patients, the mechanisms by which HIV-1 contributes to these abnormalities are poorly understood. Hemapoietic suppression can be mediated by HIV-1 and some of its associated proteins. We have previously reported that AIDS peripheral blood sera inhibit normal CFU-granulocyte macrophage (GM). In this study, we have found that sera obtained from AIDS BM patients are more inhibitory to CFU-GM than those from peripheral blood (p < 0.05). To determine a candidate suppressor factor, we studied the role of p24 and found that it exerts varying degrees of suppression to CFU-GM, but minimal inhibition on erythroid colonies. We have found that the suppressive levels of p24 in in vitro assays are similar to the average circulating levels in AIDS patients. We have also observed that most of the inhibition caused by p24 is mediated by soluble factor(s) produced by the BM stroma. Cross-linking studies with membrane proteins from normal BM stroma and CD34+ cells indicated a putative 26-kDa p24 receptor, indicating that p24 binds to a receptor present on normal BM cells. These results implicate another HIV-1 protein, p24, in hemapoietic suppression and add another plausible mechanism by which HIV-1 contributes to BM failure in AIDS. Furthermore, these findings suggest a potential risk for similar in vivo suppression in the early phase of HIV-1 infection when viremia is elevated, and also in long-term survivors who have low, although persistent, HIV-1 replication.
Department of Medicine, UMD-New Jersey Medical School, Newark, USA.
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Rameshwar
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Denny
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Gascón
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000150:complications / Q000503:physiopathology* / Q000821:virology; D000273:Adipose Tissue / Q000503:physiopathology; D001853:Bone Marrow / Q000821:virology*; D001855:Bone Marrow Diseases / Q000209:etiology*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003238:Connective Tissue / Q000503:physiopathology; D004921:Erythropoietin / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007377:Interleukin-3 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology
D016655:HIV Core Protein p24; D007074:Immunoglobulin G; D007377:Interleukin-3; D011994:Recombinant Proteins; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor