Productive infection of CD34+-cell-derived megakaryocytes by X4 and R5 HIV-1 isolates.
The human immunodeficiency virus (HIV-1) causes various hematopoietic abnormalities, with thrombocytopenia (TP) occurring in 30% of infected individuals. In the present study, we aimed to determine whether HIV-1 in the bone marrow of TP patients can infect primary megakaryocytes in vitro, which may contribute to the development of thrombocytopenia. We amplified the V3 loop of HIV-1 envelope from the bone marrow of TP and non-TP patients and constructed recombinant viruses. We demonstrate that the bone marrow of TP and non-TP patients contained R5 strains, whereas X4 strains were present only in the bone marrow of TP patients. Furthermore, HIV-1 from the bone marrow of TP and non-TP patients infected megakaryocytes to similar levels, suggesting that the V3 loop of HIV-1 may not contain the viral determinants of HIV-associated TP. Chemokine receptor analysis determined that CD34+-cell-derived megakaryocytes express CD4, CXCR4, and CCR5 and are productively infected by both X4 and R5 HIV-1 isolates. Finally, we showed that CD34+-cell-derived megakaryocytes express the chemokine receptor CCR3.
Voulgaropoulou
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F
Departments of Medicine, Pathology, and Molecular Microbiology, Washington University, St. Louis, MO 63110, USA.
Pontow
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Ratner
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L
D018952:Antigens, CD34 / Q000032:analysis*; D001853:Bone Marrow / Q000821:virology*; D015704:CD4 Antigens / Q000032:analysis; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D015658:HIV Infections / Q000150:complications / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D019707:Receptors, Chemokine / Q000032:analysis; D015728:Receptors, HIV / Q000032:analysis; D013921:Thrombocytopenia / Q000150:complications / Q000821:virology; D014779:Virus Replication
D018952:Antigens, CD34; C515350:CCR3 protein, human; D015704:CD4 Antigens; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D015728:Receptors, HIV