Productive infection of CD34+-cell-derived megakaryocytes by X4 and R5 HIV-1 isolates

Virology. 2000 Mar 30;269(1):78-85. doi: 10.1006/viro.2000.0193.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD34 / analysis*
  • Bone Marrow / virology*
  • CD4 Antigens / analysis
  • Cells, Cultured
  • Cloning, Molecular
  • Fluorescent Antibody Technique
  • HIV Infections / complications
  • HIV Infections / virology
  • HIV-1 / classification
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • HIV-1 / physiology*
  • Humans
  • Megakaryocytes / cytology
  • Megakaryocytes / immunology*
  • Megakaryocytes / virology*
  • Receptors, CCR3
  • Receptors, CCR5 / analysis
  • Receptors, CXCR4 / analysis
  • Receptors, Chemokine / analysis
  • Receptors, HIV / analysis
  • Thrombocytopenia / complications
  • Thrombocytopenia / virology
  • Virus Replication

Substances

  • Antigens, CD34
  • CCR3 protein, human
  • CD4 Antigens
  • Receptors, CCR3
  • Receptors, CCR5
  • Receptors, CXCR4
  • Receptors, Chemokine
  • Receptors, HIV