Infection of megakaryocytes by human immunodeficiency virus in seropositive patients with immune thrombocytopenic purpura

Abstract

Twenty-one human immunodeficiency virus (HIV)-positive patients, including 11 acquired immunodeficiency syndrome (AIDS)-free patients with immune thrombocytopenic purpura (ITP), were studied to determine whether the megakaryocytic/platelet lineage was infected by HIV. Because purification of platelets did not reach a level sufficient for unequivocal results by the polymerase chain reaction, in situ hybridization was thus performed. Purified marrow megakaryocytes (MK) from 10 HIV-infected ITP patients were studied using a 35S HIV riboprobe, antisense of an HIV ENV sequence. HIV transcripts were clearly detected in MK from five of these 10 patients, although heterogeneity among MK was observed. In three of these five cases, small amounts of HIV glycoproteins were detected in MK by means of immunofluorescence. In addition anti-HIV antibodies could be eluted from platelets of all patients. In contrast, HIV transcripts were not detected in MK derived from colony-forming units-MK (CFU-MK) cultured in suspension, suggesting either that MK are infected by HIV during terminal differentiation or that HIV-infected CFU-MK are unable to differentiate in vitro. In conclusion, this study suggests that HIV infection of MK may be implicated in the pathogenesis of thrombocytopenia of HIV-positive patients.

Association of autoantibodies against platelet glycoproteins Ib/IX and IIb/IIIa, and platelet‐reactive anti‐HIV antibodies in thrombocytopenic narcotic addicts

“…Another possible mechanism that may account for the occurrence of antiplatelet antibodies in HIV patients is the presence of specific HIV antigens on the platelet membrane due to an HIV infection of the megakaryocyte/platelet lineage. In support of this hypothesis, it has been reported that human megakaryocytes have a functional CD4 molecule capable of binding HIV (Kouri et al, 1993), and that megakaryocytes from HIV-infected thrombocytopenic patients express HIV transcripts or proteins (Zucker-Franklin & Cao, 1989;Louache et al, 1991). However, whether human megakaryocytes are truly infected by HIV, i.e.…”

The development of human megakaryocytes. II. CD4 expression occurs during haemopoietic differentiation and is an early step in megakaryocyte maturation

“…Thrombooiesisand/or megakaryocytopoiesis could be impaired either by direct infection of CD4 MK progenitors or by an indirect mechanism involving altered cytokine production by an infected accessory cell. A variety of evidence has been offered to suggest that cells of the MK lineage can be infected by HIV-1 (Zucker-Franklin et al, 1989;Kouri et al, 1993;Sakaguchi et al, 1991;Louache et al, 1991;Zucker-Franklin & Cao, 1989).…”

Platelet Chemokines and Chemokine Receptors: Linking Hemostasis, Inflammation, and Host Defense

“…This decreased production of platelets may be caused by bone marrow infiltration of opportunistic infection or malignancy, or by HIV-1 infection of platelet precursors. HIV-1 can infect megakaryocytes in vitro and has been detected in megakaryocytes isolated from patients with HIV-1 TP (25,95,106,162). Because megakaryocytes and their precursors express CD4 and CXCR4, but not CCR5, there should be a preponderance of CXCR4-tropic HIV-1 (X4 HIV-1) or dual tropic HIV-1 (R5X4 HIV-1) in the bone marrow of patients with HIV-1 TP (24).…”